ESMO Supporter 2018

Displaying One Session

Hall A3 - Poster Area Networking Hub Poster Display session
Date
22.10.2018
Time
12:45 - 13:45
Location
Hall A3 - Poster Area Networking Hub
Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

Breast cancer, early stage

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

194P - Real-Life Utilization of Genomic testing for invasive Breast Cancer patients in Italy and France reduces Chemotherapy Recommendations

Presentation Number
194P
Lecture Time
12:45 - 12:45
Speakers
  • Sandro Barni (Treviglio, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Oncotype DX® (ODX) is a multigene assay allowing physicians to tailor treatment in HR+, HER2- early-stage breast cancer patients. Clinical validation and utility of ODX have been demonstrated across multiple studies in over 63,000 breast cancer patients worldwide. It provides level 1A evidence and has been incorporated in major international clinical guidelines. A market access program was initiated in 2015 in France and 2016 in Italy to assess real-life test utilization and its impact in current clinical practice.

Methods

The program allows for prospective data collection reflecting real life use of ODX by physicians in various clinical practice settings throughout France and Italy. Patient data were collected through an online dedicated platform including classical pathological and clinical parameters (e.g. histology, tumor grade and size, ER, PR, HER2 and Ki67), patient age, ODX Recurrence Score (RS) Results and recommended treatment both before and after the test results have been reported.

Results

A total of 53 and 19 qualified breast cancer centers, in France and Italy respectively, participated in the program and collected 2632 case reports. Study results demonstrated that ODX is used among a wide variety of patient profiles: 24% N1, 7% Nmic & 69% N0, 11% G1, 64% G2 and 25% of G3, 32% pre-, 8% peri- & 59% are post-menopausal, 34% are 35-50, 52% 51-70 and 13% are older than 70, 13% have Ki67%<10%, 35% KI67 10-20%, 30% KI67 21-30% & 18% Ki67>30%, 12% tumor <1cm, 59% 1-2cm and 27% tumor 2.1-5cm. RS distribution is the following: <18 (56%), 18-30 (35%) and >30 (9%). In addition, pre-ODX 60% and 48% patients had a treatment recommendation for chemo-hormonotherapy (CT-HT) in France and Italy respectively. Post-testing, the number of patients recommended CT-HT decreased to 29% and 31% for France and Italy respectively, highlighting that the test reduced unnecessary use of CT and homogenized treatment decisions.

Conclusions

In France and Italy, the use of the ODX test results in an overall reduction in CT recommendations, while also identifying patients more likely to benefit from CT.

Legal entity responsible for the study

Genomic Health SARL.

Funding

Genomic Health SARL.

Disclosure

S. Barni, F. Cognetti: Medical Consultant: Genomic Health. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

195P - Benefit of adjuvant chemotherapy in hormone receptor-positive, HER2-negative, invasive lobular carcinoma of the breast

Presentation Number
195P
Lecture Time
12:45 - 12:45
Speakers
  • Alexandre De Nonneville (Marseille, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Invasive lobular carcinoma (ILC) is the second most common histologic breast cancer subtype and represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) in ILC is still unclear.

Methods

Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,537 patients who underwent primary surgery in 18 French centres between 1990 and 2014. Only ILC, hormone-positive, HER2-negative patients who received adjuvant endocrine therapy (ET) were included. Endpoints were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT was estimated using a logistic regression including age, tumour size, nodal status, lymphovascular invasion (LVI), grade, type of surgery, period and CT.

Results

Of a total of 2,318 patients with ILC, 1,485 patients (64%) received ET alone and 823 (36%) received ET+CT. Patients receiving ET+CT had more adverse prognostic features, such as young age, larger tumour size, high grade, macroscopic lymph-node involvement and LVI, received more adjuvant radiotherapy and underwent more often mastectomy. In a multivariate Cox model, we observed a beneficial effect of addition of CT to ET on both DFS and OS, (HR = 0.61, 95% CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score-matching, aiming to compensate for baseline characteristics, was used. Ten-year estimates DFS in case-matched patients for propensity score analysis were 90% (95% CI [87%-93.4%]) in the ET+CT group vs. 66% (95% CI [61.4%-71.4%]) with ET alone and 10-year estimates OS were 96% (95% CI [93.8%-98%]) in the ET+CT group vs. 71% (95% CI [66.6% et 76.2%]) with ET alone. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT.

Conclusions

Patients receiving adjuvant ET for hormone receptor-positive, HER2-negative ILC could derive significant DFS and OS benefits from CT. Our results highlight that patients with high-risk ILC should not be denied adjuvant CT because of such histologic subtype.

Legal entity responsible for the study

Gilles Houvenaeghel.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

196P - Baseline lymphocyte counts predict distant recurrence in early breast cancer

Presentation Number
196P
Lecture Time
12:45 - 12:45
Speakers
  • Gun Min Kim (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The presence of pretreatment lymphopenia or high NLR (neutrophil-lymphocyte ratio) has been reported as poor prognostic factor in breast cancer. Here, we investigated whether baseline lymphocyte counts and NLR are associated with overall survival (OS), breast cancer specific survival (BCSS), and distant recurrence free survival (DRFS) in large early breast cancer (EBC) patient cohort.

Methods

We reviewed demographic, clinical, pathologic, and survival data from Yonsei Breast Cancer Center Registry. Patients who underwent surgery with stage I-III EBC at the Yonsei Cancer Center between 2006 and 2015 were included. Baseline complete blood counts data were collected from electronic medical records system. Multivariable regression models adjusted for age, stage, neoadjuvant/adjuvant chemotherapy use, subtype were used to evaluate associations between baseline absolute lymphocyte count (ALC) and OS/BCSS/DRFS.

Results

A total of 5,785 stage I–III EBC patients were underwent breast surgery from 2006 to 2015; 533 patients were excluded due to lack of complete data (n = 262) and the diagnosis of second primary cancer (n = 270). Median follow up duration was 72.73 months (95% confidence interval (CI), 73.85-75.64). Of 5,252 eligible patients, only 159 (3.0%) had baseline lymphopenia (ALC < 1,000/mL). The incidence of baseline lymphopenia was similar among age group, stage, and subtype, but patients with HBsAg (+) showed higher baseline lymphopenia than HBV negative patients (7.7% vs. 2.9%, p = <0.001). In univariate analysis, baseline lymphopenia was significantly associated with poor OS, BCSS and DRFS. In multivariable analysis, baseline lymphopenia predicted lower DRFS [HR 0.502; 95% CI, 0.307–0.820]. The prognostic significance of baseline lymphopenia regarding to DRFS was highest in HER2 positive subtype.

Baseline demographics

All Patients (n = 5,252)Baseline Lymphopenia (n = 158)No Baseline Lymphopenia (n = 5,094)
Age
Median (Range)50 (19-92)48 (31-77)50 (19-92)
TNM Stage
I2672 (50.9)81 (51.3)2591 (50.9)
II1890 (36)53 (33.5)1837 (36.1)
III450 (8.6)18 (11.4)432 (8.5)
Subtype
ER+/HER2-3286 (62.6)90 (57)3196 (62.7)
ER+/HER2+558 (10.619 (12)539 (10.6)
ER-/HER2+496 (9.4)22 (13.9)474 (9.3)
ER-/HER2-912 (17.4)27 (17.1)885 (17.4)
Neoadjuvant chemotherapy
Yes983 (18.7)124 (78.5)4145 (81.4)
No4269 (81.3)34 (21.5)949 (18.6)
Adjuvant chemotherapy
Yes2957 (56.3)69 (43.7)2226 (43.7)
No2295 (43.7)89 (56.3)2868 (56.3)
Radiation therapy
Yes3755 (71.5)49 (31)1448 (28.4)
No1497 (28.5)109 (69)3646 (71.6)
Endocrine therapy
Yes3799 (72.3)108 (68.4)3691 (72.5)
No1453 (27.7)50 (31.6)1403 (27.5)
HBsAg test
Positive182 (3.5)14 (8.9)168 (3.3)
Negative4419 (84.1)126 (79.7)4293 (84.3)
Unknown651 (12.4)18 (11.4)633 (12.4)
Baseline Lymphopenia
Yes158 (3)
No5094 (97)

Conclusions

Baseline lymphocyte counts predicted distant recurrence in early breast cancer.

Legal entity responsible for the study

Gun Min Kim.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

197P - A propensity score analysis exploring the impact of the addition of adjuvant chemotherapy (aCT) to hormone therapy (aHT) in a multi-center series of resected luminal early stage pure Invasive Lobular Breast Carcinoma (ILC).

Presentation Number
197P
Lecture Time
12:45 - 12:45
Speakers
  • Luisa Carbognin (Verona, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Patients (pts) resected for luminal early breast cancer are assigned to receive aCT according to international guidelines based upon clinico-pathological features, regardless of the histotype, given the lack of prospective data for ILC. Thus, the magnitude of the benefit of the addition of aCT to aHT for ILC is still not sizable. The aim of this analysis was to investigate the effect of aCT in a multi-center series of luminal early stage pure ILC.

Methods

Clinico-pathological data of consecutive pts affected by luminal pure ILC, undergone surgery between 2000 and 2014, were correlated with disease-free and overall survival (DFS/OS) using a Cox model. A propensity score analysis was performed to evaluate the prognostic impact of aCT. Kaplan-Meier curves were compared with Log-Rank analysis.

Results

Data from 576 pts were gathered (median age 58 years (yrs)). At median follow-up of 72 months, 5-/10-yrs DFS and OS were 81.5%/71.8% and 91.8%/80.4%, respectively. Tumor-size according to TNM (T, HR 1.78, 95% CI 0.91-3.49, p = 0.09) and lymph-node (N) status (HR 2.97, 95% CI 1.69-5.19, p < 0.0001) were independent predictors for DFS at multivariate analysis. N status (HR 3.93, 95% CI 1.79-8.70, p = 0.001), Ki67 (HR 2.66, 95% CI 0.92-7.70, p = 0.072), and age (HR 2.32, 95% CI 1.09-4.93, p = 0.029) were predictors for OS. A significant prognostic effect of aCT upon OS was found after adjusting for T, N, Ki67, grading and age at diagnosis with the propensity score method, as shown in the table. Particularly, aCT significantly prolongs DFS in pts with T > 2 (p = 0.03) and OS in pts with Ki67 >4% (p < 0.0001).

OutcomeCategory5-yrs (%)10-yrs (%)Log-Rank
DFSaHT76.654.4p = 0.08
aCT + aHT85.076.4.
OSaHT80.955.6p = 0.001
aCT + aHT98.195.9

Conclusions

Despite the retrospective nature of this analysis, the propensity score analysis indicates that pts with luminal ILC may significantly benefit from the addition of aCT to aHT in terms of long-term survival, particularly for larger and more aggressive tumors.

Legal entity responsible for the study

University of Verona.

Funding

University of Verona.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

198P - Benefit of Adjuvant Systemic Therapies in HR+ HER2- pT1ab Node-Negative Breast Carcinomas

Presentation Number
198P
Lecture Time
12:45 - 12:45
Speakers
  • Alexandre De Nonneville (Marseille, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Hormone receptor-positive, HER2-negative, pT1ab N0 breast cancers (BC) are generally estimated as having a low risk of recurrence after locoregional treatment and adjuvant treatment decisions could be challenging. We examined the impact of endocrine therapy (ET) +/- chemotherapy on outcomes in this population.

Methods

A total of 4,788 patients with pT1ab N0 HR+ HER2- BC were identified from a large cohort of 22,475 consecutive patients who underwent primary surgery at 15 French centres between 2000 and 2014. Endpoints were disease-free survival (DFS) and overall survival (OS). Analyses of causal effect using propensity scores were realized using a logistic regression including age, tumour size, histology, grade, and lymphovascular invasion (LVI).

Results

Of 4,779 patients with pT1ab HR+ HER2- BC, 846 patients did not receive any adjuvant treatment and 3,933 received ET, among which 251 received chemotherapy. Age ≥ 70y, ductal histology, high grade and tumour size > 5mm were independently associated with ET prescription. Age ≤ 40y, LVI and high grade, were independently associated with chemotherapy prescription. At a median follow-up of 47.7 months, ET was independently associated with a significant DFS benefit in multivariate analysis (HR: 0.60 [0.41-0.89]; p = 0.011) with 5-year estimate DFS of 94% (CI95 [92-96%]) without ET vs. 96% (CI95 [95-97%]) with ET, while addition of adjuvant chemotherapy was not (HR: 0.90 [0.39-2.09]; p = 0.813). These results were supported by the analyses of causal effect using propensity scores (HR: 0.48 [0.28-0.83]; p = 0.009 for ET, and HR: 1.54 [0.11-21.8]; p = 0.78 for chemotherapy). OS was not significantly impacted by systemic treatments despite a trend for ET in multivariate (HR: 0.60 [0.36-1.00]; p = 0.051) and in propensity score analyses (HR: 0.52 [0.24-1.11]; p = 0.092).

Conclusions

Adjuvant endocrine therapy is associated with a survival benefit in pT1ab N0 HR+ HER2- BC even with a relatively short follow up. Consistent with current consensus guidelines that do not recommend adjuvant chemotherapy in these tumours, we did not find any benefit of adding chemotherapy to ET. These data provide additional clues to the issue of adjuvant systemic treatments in these tumours.

Legal entity responsible for the study

Gilles Houvenaeghel.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

199P - Anti-proliferative effect of oral metronomic vinorelbine in PAM50 Luminal/HER2-negative early breast cancer (SOLTI-1501 VENTANA): an open-label, randomized, three-arm, multicenter, window-of-opportunity study

Presentation Number
199P
Lecture Time
12:45 - 12:45
Speakers
  • Aleix Prat (Barcelona, ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The anti-proliferative effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor (HR)-positive/HER2- breast cancer has been scarcely addressed.

Methods

Postmenopausal women with untreated stage I-III breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5mg/day, oral mVNB 50mg 3 days/week or the combination. The 1ary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of mVNB+LTZ was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene Proliferation Score in each arm. 2ary objectives included safety and the comparison of the anti-proliferative effect between arms. An unplanned analysis of stromal tumor infiltrating lymphocytes (TILs) was performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360TM panel.

Results

A total of 61 patients were randomized and 54 paired samples (89%) were analyzed. Main patient characteristics were mean age 67, mean tumor size 1.7 cm, stage I (55.7%) and grade 1-2 (90%). Grade 3 toxicities occurred in 3.3% of cases. Most baseline samples were Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of mVNB+LTZ (-73.2%) was superior to both monotherapy arms combined (-49.9%; p = 0.001) and mVNB (-19.1%; p < 0.001). The anti-proliferative effect of mVNB+LTZ (-73.2%) was higher compared to LTZ (-65.7%) but did not reach statistical significance (p = 0.328). Stromal TILs (≥10% at week 3) were observed across arms in 6.6% (mVNB), 15% (LTZ) and 26% (mVNB+LTZ) of the cases. In tumors with ≤10% TILs at baseline, a significant increase in TILs was observed following VNB+LTZ (paired analysis p = 0.012).

Conclusions

mVNB is well-tolerated and presents antiproliferative activity alone and in combination with LTZ. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. Of note, the increase of TILs observed with the combination opens the possibility of studying this combination with immunotherapy.

Clinical trial identification

NCT02802748.

Legal entity responsible for the study

SOLTI Breast Cancer Research Group.

Funding

Pierre Fabre Médicament.

Disclosure

A. Prat: Consultancy: Pfizer, Eli Lilly, Novartis, Nanostring Technologies; Research funding: Novartis, Nanostring Technologies; Scientific advisory board: Oncolytics Biotech. J.A. Perez Fidalgo: Advisory board: Clinigen, Pharmamar, Clovis; Other: Substantiate relationships (speaker) Roche, Pharmamar, AstraZeneca, Ipsen. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

200P - Clinicopathologic significance of androgen receptor expression and discordant receptor status during progression in breast cancer

Presentation Number
200P
Lecture Time
12:45 - 12:45
Speakers
  • Chan Heun Park (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The role of androgen receptor (AR) as a prognostic marker has been proposed in breast cancer. This study investigated AR status and its clinical significance in breast cancer, especially in triple negative breast cancer (TNBC). We also evaluated discordant AR status during the process of lymph node metastasis, locoregional recurrences (LRR) and distant metastasis.

Methods

From January 2005 to December 2010, we retrospectively reviewed 120 patients including 55 TNBC patients diagnosed as invasive carcinoma with no special type (NST), who were treated at the Kangbuk Samsung Hospital. Tissue microarray was constructed and immunohistochemical expression of AR was performed for 120 invasive carcinomas, NST specimens and matching samples from 28 lymph node metastasis, 2 LRR and 8 distant metastases.

Results

AR expression was found in 35.0% (42/120) of the total patients and 14.5% (8/55) of those diagnosed as TNBC. Positive expression of AR was significantly correlated with smaller tumor size, early T stage, fewer lymph node metastases, early AJCC stage, lower histologic grade, estrogen receptor/progesterone receptor positivity, more luminal A type, less TNBC, longer disease-free survival and overall survival, fewer distant metastasis and no deaths from breast cancer (all P < 0.05). AR was a favorable prognostic marker for disease free survival in univariate analysis (P = 0.041). The discordance rate of AR status between primary and recurrent/metastatic disease was 21.6%.

Conclusions

AR expression was associated with favorable clinicopathological outcomes in the whole study population. AR status can be altered during tumor progression.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

201P - The outcomes of early breast cancers utilizing the Oncotype Dx Recurrence score (RS) instead of Clinico-pathological (CP) factors for prognostic risk assessment: A Single Institution Experience

Presentation Number
201P
Lecture Time
12:45 - 12:45
Speakers
  • Adhar D. Alsayed (Riyadh, SA)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Genomic profiling of hormone receptor positive breast cancer outperforms CP factors in predicting the outcomes. This has led to wider application of genomic testing for risk stratification. This can lead to avoidance of chemotherapy in patients with favorable outcomes.

Methods

Patient with T1, T2, node negative estrogen and or Progesterone receptor positive Her 2 Negative breast cancer, regardless of age, menopausal status, Grade or Ki67 were eligible for risk prediction using the Oncotype DX RS. All patient who had RS were included from March 2012- September 2017. The test was sent out and done in reference laboratory (Genomic Health). The original cut off of Low RS (<18), Intermediate RS18-31 and high RS > 31 was used. Patient with low RS were spared chemotherapy. While those high score received chemotherapy. Intermediate risk was preferably given chemotherapy. The changes in therapy based on RS score were reordered as compared to CP factors (St. Gallen Criteria). The disease free and overall survival was analyzed.

Results

Complete data was available for 141 Patients. Median age was 51 years (30-78). 54% premenopausal. 97% ductal histology. Grade correlated with RS with higher grade having higher RS. There was 67% reduction in use of adjuvant chemotherapy when compared to decision based on CP factors while 1 patient had escalation of therapy based on RS. Median follow up was 32 months (3-73 months). The 5 year estimated DFS was 95%. The overall survival was 98%. Only recurrence score correlated with DFS p = 0.04 while age, Ki67, grade, tumor size did not.

Conclusions

Our data in a younger group of mainly premenopausal women with early breast cancer is consistent with the published date about the prognostic value of RS. A substantial percentage of these patient can be spared chemotherapy and its related toxicity without adversely affecting the long-term outcomes. Utilizing RS in decision making may potentially be cost effective.

Legal entity responsible for the study

The breast cancer group at KFSH.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

202P - Circulating tumor cells as a prognostic marker in non metastatic breast cancer patients.

Presentation Number
202P
Lecture Time
12:45 - 12:45
Speakers
  • Summar M. Elmorshidy (Assiut, EG)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Still, there is no clinically reliable marker to detect micro-metastasis or breast cancer relapse. This study aimed to evaluate the role of circulating tumor cells (CTCs) as a biomarker in non-metastatic breast cancer patients.

Methods

CTCs quantification was carried out using flow cytometry for 50 breast cancer patients post-operatively on three intervals; before starting, after three cycles and at the end of adjuvant chemotherapy. The relationship between CTCs and other tumor characteristics and outcomes were studied.

Results

The median follow-up duration was 35 months. Before starting adjuvant chemotherapy, CTCs were positive (cut off point ≥5) in 36% of the patients and dropped to 20% after finishing chemotherapy (P = 0.04). There was a strong negative correlation (r=-0.89) between change in the CTC levels from baseline till mid-treatment (3 cycles) and from this point to the end of treatment (6 cycles) (R2=79.2). CTCs were detected in 88.9% (n = 16 of 18) of node-positive patients and in 11.1% of node-negative patients (n = 2 of 18, p-value =0.04). No significant association was found with tumor size, grading, or hormone receptor status. Distant metastasis was detected in 20% (n = 10 of 50) of patients and was significantly associated with CTCs ≥ 5 in 80 % of them (n = 8 of 10) p-value =0.01. The presence of ≥ 5 CTCs at baseline was associated with reduction in both the disease-free survival and overall survival (p-value <0.001 and =0.003, respectively) . Baseline CTCs ≥5 were confirmed as an independent prognostic factor in multivariate cox hazard regression analysis for DFS (HR = 3.71; 95% CI = 1.62-8.48; p-value=0.002 and OS (HR = 3.14; 95% CI = 1.34-7.37;p-value= 0.009).

Conclusions

The findings of the current work suggested that the presence of ≥ 5 CTCs at baseline would predict early disease recurrence and reduce the overall survival in primary, non-metastatic breast cancer patients receiving adjuvant chemotherapy. Thereby, peripherally detected CTCs could be used as a new prognostic marker for identification of early relapse and survival reduction.

Legal entity responsible for the study

Assiut University, Egypt.

Funding

Assiut University Hospitals, Egypt.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

203P - Molecular subtyping of breast cancer by dedicated breast PET

Presentation Number
203P
Lecture Time
12:45 - 12:45
Speakers
  • Satoshi Sueoka (Hiroshima, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Therapeutic strategies for treating breast cancer differ according to molecular subtype. We investigated whether dedicated breast PET (DbPET), a high-resolution molecular breast imaging system, could stratify breast cancer by subtype.

Methods

We included 390 patients with invasive breast cancer who underwent ring-type DbPET between January 2016 and March 2018. The association between SUVmax and various tumor characteristics such as size, nuclear grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and Ki-67 labeling index, were assessed. Tumor subtypes were classified as luminal A-like, luminal B-like, ER+/HER2+, ER-/HER2+, or triple negative on the basis of the St. Gallen International Expert Consensus.

Results

The median patient age was 57 years, the median tumor size was 1.5 cm, and the median SUVmax on DbPET was 6.9. The number of patients with each subtype was luminal A-like in 113, luminal B-like in 185, ER+/HER2+ in 40, and ER-/HER2+ in 12, and triple negative in 40 patients. SUVmax significantly correlated with tumor size (P < 0.001), nuclear grade (P < 0.001), ER status (P = 0.004), HER2 status (P < 0.001), and Ki-67 labeling index (P < 0.001). The median SUVmax values of the luminal A-like, luminal B-like, ER+/HER2+, ER-/HER2+, and triple negative subtypes were 4.6, 8.2, 9.5, 16.1, and 10.4, respectively (Table, all values of P < 0.001 relative to luminal A-like). Thus, DbPET distinguished luminal A-like tumor subtype from other subtypes.

SUVmax on dedicated breast PET according to molecular subtypes.
SubtypesMedian SUVmax (IQR)P value reffered to luminal A-like
Luminal A-like4.6 (3.0-6.8)
Luminal B-like8.2 (4.6-12.4)< 0.001
ER+/HER2+9.5 (5.5-16.6)< 0.001
ER-/HER2+16.1 (7.5-20.2)< 0.001
Triple negative10.4 (4.2-17.0)< 0.001

Conclusions

DbPET can be used to classify breast cancer into molecular subtypes, which may help determine the necessity of adjuvant chemotherapy. SUVmax, as assessed on DbPET, may thus contribute to the selection of proper therapeutic strategies in invasive breast cancer.

Legal entity responsible for the study

Hiroshima University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

204P - Analytical validation of OncoMasTR, a multigene test for predicting risk of distant recurrence in hormone receptor-positive early stage breast cancer

Presentation Number
204P
Lecture Time
12:45 - 12:45
Speakers
  • Tony Loughman (Dublin, IE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

OncoMasTR is a new multigene prognostic test that was discovered via a novel transcriptional network analysis method that identified upstream Master Transcription Regulators (MTRs), which regulate previously identified prognostic biomarkers. The optimised OncoMasTR signature incorporating clinicopathological information has been shown to be significantly prognostic for predicting distant recurrence in two independent cohorts (TransATAC & a subset of TAILORx from participating Irish centres). The analytical performance characteristics of the OncoMasTR test, comprising solely three prognostic MTRs, were determined.

Methods

Relative gene expression levels were measured by RT-qPCR. Assay precision and input ranges were determined using a panel of samples representative of low and high recurrence risk tested across a number of runs incorporating different sources of variation. Serial dilutions of a pooled patient RNA sample was used to establish the linear range and efficiency of the individual gene assays.

Results

The overall standard deviation of the OncoMasTR risk score was 0.15, which represents less than 2% of the 10-unit risk score range. The majority of the variability in OncoMasTR results was related to within-run variation (78.2%) with other between-run variation sources contributing relatively little (PCR instrument (0.6%), assay operator (5.2%), reagent lots (7.3%) or loading position (8.7%)). Consistent risk scores were measured for individual samples from 40ng down to < 1ng RNA per PCR reaction. Individual gene assays were linear over >500-fold RNA input range corresponding to CT values of 23 – 36, demonstrating the ability of the test to reliably detect low level expression of the OncoMasTR panel. Importantly, PCR efficiencies were similar for the individual MTR and reference gene assays which ranged from 79 – 95%.

Conclusions

The OncoMasTR prognostic test displays robust analytical and clinical performance and is being launched as a CE-marked test. The concise nature of the three gene signature and a simplified workflow that can be readily adopted using standard laboratory equipment will enable convenient qualification by local laboratories for decentralised use.

Legal entity responsible for the study

OncoMark Limited.

Funding

EU Horizon 2020 SME Instrument.

Disclosure

T. Loughman, A. Chan-Ju Wang, P. Dynoodt, B. Fender, C. Lopez Ruiz, S. Barron, S. Stapleton: Employee: OncoMark Limited. D. O’Leary, W.M. Gallagher: Director and shareholder: OncoMark Limited. A. Fabre, C. Quinn: Consultant histopatholgist: OncoMark Limited. A. Bracken: Co-inventor and patent holder for OncoMasTR. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

205P - Comparing the prognosis of favourable-histology breast cancers between younger women of less than 45 years of age at diagnosis with their older counterparts.

Presentation Number
205P
Lecture Time
12:45 - 12:45
Speakers
  • Guek Eng Lee (Singapore, SG)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Tubular, cribriform and mucinous carcinomas account for <10% of all breast cancer histology. They have excellent prognosis and aggressive treatment with chemotherapy is usually not warranted. Younger age at breast cancer diagnosis is often associated with a poorer prognosis in early breast cancers, however little is known about the natural history of favourable-histology breast cancers for younger women compared to their older counterparts. We aim to compare the prognosis of younger women less than 45 years of age with their older counterparts for early breast cancers with favourable histology.

Methods

Using the SEER dataset from 1988-2015, we identified 20 577 women diagnosed with early stage breast cancers of favourable histology i.e. tubular, cribriform, and mucinous carcinoma. We extracted the information on age of diagnosis, estrogen receptor (ER) status, progesterone receptor status (PR), HER2 status, ethnicity, cause of death, and survival months. The survival was compared between women < 45 years of age at diagnosis versus ≥ 45 years using log-rank test and cox-regression to give a univariate and multi-variate analysis.

Results

Among 20577 women with early stage favourable-histology breast cancers, we identified 1308 (6.4%) tubular, 6486 (31.5%) cribriform, and 12 783 (62.1%) mucinous breast cancer. The median age of diagnosis is 42 and 64 years of age for the younger group of < 45 years of age and older group of ≥ 45 years of age respectively. 85% of the breast cancer in younger women were ER+ while 88% in the older age group were ER+. In a univariate analysis, the median breast cancer specific survival for early stage favourable histology breast cancer was 120 months for women < 45 years of age and 100 months for women ≥ 45 years of age (p < 0.001). In multi-variate analysis, accounting for tumour size, nodal status, stage, grade, hormone receptor status, HER2 receptor status, histologic type and year of diagnosis, younger age still predicts for a better outcome (p < 0.001).

Conclusions

Younger women diagnosed with early stage favourable-histology breast cancers have a better prognosis compared to older women. This will help in counselling on prognosis and management of younger patients.

Legal entity responsible for the study

Guek Eng Lee.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

206P - TNBC universe: a monocentric retrospective analyses of TILs and AR as prognostic markers

Presentation Number
206P
Lecture Time
12:45 - 12:45
Speakers
  • Agnese Losurdo (Milan, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

TILs have been proposed as a prognostic biomarker in many tumor types both in the adjuvant and neoadjuvant setting. In TNBC, TILs are present at the highest level and have been demonstrated to be associated with better prognosis. TNBC is a highly diverse group of cancers and subtyping is necessary to better identify patient-tailored therapies. Cluster analysis by gene expression identified 6 TNBC subtypes among which the so called “luminal androgen receptor subtype”.

Methods

We retrospectively collected 160 early stage TNBC consecutively treated at our Institution from 2006 to 2015. Data were obtained for clinico-pathological patients' characteristics. On IHC archive slides we analyzed stromal TILs scored as a continuous variable and androgen receptor's (AR) percentage and intensity of expression. We performed Cox analyses for DFS and for OS, and we used chi-square and Fisher test to evaluate the correlation between TILs, AR and other clinical variables. To define high vs low TILs, an internal dataset cut-off of 10% was considered.

Results

150 patients were eligible for IHC analyses of TILs and AR. With a median follow-up of 6.5 years, 41 local and/or distant relapse events were observed and 28 patients died of disease. Interestingly, TILs were found to be significantly associated with nodal status (N0 vs N1-3), grading (G2 vs G3) and Ki-67 (<20% vs ≥ 20%) (p = 0.007, p = 0.055 and p = 0.002, respectively). AR was also significantly associated with proliferation, specifically AR-positive cases presented mostly with a Ki-67<20% (p = 0.008). Probably due to the paucity of events, no statistically significant association of TILs and AR with either DFS or OS was observed.

Conclusions

TILs are a promising prognostic marker, but still prospective validation is needed to integrate them into clinical practice. Among TNBC, the identification of AR-expressing luminal subtype might provide a targeted therapy chance for a low proliferation TNBC subtype. Larger prospective trials are likely to validate TILs prognostic role and to explore the universe of TNBC subtypes targeted therapies opportunities.

Legal entity responsible for the study

Istituto Clinico Humanitas.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

207P - Genomic spectrum of Asian breast cancer based on targeted next-generation sequencing in 150 consecutive primary breast cancer

Presentation Number
207P
Lecture Time
12:45 - 12:45
Speakers
  • Chihwan Cha (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Application of next-generation sequencing (NGS) enables to reveal genetic diversity of malignant tumors. Here we report our experience with targeted NGS in Asian patients with primary breast cancer.

Methods

We identified 150 Asian patients who had genotyping by targeted NGS between April 2017 and Mar 2018 in a single institution. The genetic mutation patterns of the patients were analyzed retrospectively. Targeted NGS with the Oncomine™ comprehensive panel including 143 genes was conducted on Ion Torrent S5 XL (Thermo Fisher Scientific, Waltham, MA, USA). All patients had stage I-III by AJCC 7th edition.

Results

Targeted NGS was conducted in a total of 150 primary breast cancer including 98 (65.3%) patients of the luminal/HER2-negative subtype, 28 (18.7%) patients of the HER2 subtype, and 24 patients of the (16.0%) TNBC subtype. Of the 150 patients, 138 patients had 432 genomic alterations including 306 mutations and 126 aberrant copy number variations (CNV). The most common genetic mutation was PIK3CA mutation (64 patients, 42.7%), followed by TP53 mutation (48 patients, 32.0%), TET2 mutation (26 patients, 17.3%) and ERBB2 mutation (6 patients, 4.0%). Of the 6 patients with ERBB2 mutations, 5 patients were in the luminal/HER2-negative subtype and 1 in the HER2 subtype. When ERBB2 amplification excluded, most common CNV was found in FGFR1 (12 patients, 8.0 %) followed by CCND1 (10 patients, 6.7 %). In 35 ER-positive/HER2-negative patients who agreed to receive Oncotype DX assay, 18 patients (48.6%) had PIK3CA mutation. In patients with PIK3CA mutation, 13 (72.2%) had a low RS, and 5 patients (27.8%) had an intermediate RS. A patient with RS of 27, which is recognized as high score by the criteria of TAILORx trial, had co-mutations as PIK3CAH1047R and P53K132N.

Conclusions

Our data with targeted NGS panel suggested that genomic landscape of Asian breast cancer is in accordance with previous NGS studies with Western women. In addition, our subgroup study with Oncotype DX supports early notion that ER-positive breast cancer patients with PIK3CA mutation show a better prognosis compared with those without PIK3CA mutation.

Legal entity responsible for the study

Chihwan Cha.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

208P - The Impact of the 21 Gene Recurrence Score (RS) on Chemotherapy (CHemoRx) Prescribing in Hormone Receptor (HR) Positive, Lymph Node Positive (LN+) Early-Stage Breast Cancer (BC) in Ireland: A National, Multi-centre, Prospective Study (CTRIAL-IE 15-34)

Presentation Number
208P
Lecture Time
12:45 - 12:45
Speakers
  • Anees Hassan (Dublin, IE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The 21 gene RS has improved the selection of patients (pts) for ChemoRx in early BC. Internationally, the RS is used in LN+ disease, but has not been reimbursed for this indication in Ireland. We conducted a prospective study to determine the extent to which use of the RS could alter Oncologists’ ChemoRx recommendations in pts with LN+ BC.

Methods

Eligible patients had 1-3 LN+, HR+ HER2- BC. All pts gave written informed consent. Baseline demographics were collected. Questionnaires were completed by a Consultant Oncologist before and after the RS, which examined expectations of tumour chemo-sensitivity, strength of ChemoRx recommendation and type of planned ChemoRx. The primary endpoint was the % reduction in pts recommended ChemoRx (N = 75).

Results

RS was available on 74/75 pts; median age 54 (range 32-78) years. Most pts had T1 (43%) / T2 (47%), grade 2 (72%) tumours with 1 LN + (68%). The RS was <11 in 10 (13%), 11-25 in 56 (76%) and >25 in 8 (11%) pts. Access to the RS led to a 27% reduction in ChemoRx recommendations from 68 (92%) to 48 (65%) pts. This was most notable in pts with 1 LN + (46 vs 24) and 2 LN + (13 vs 7). Access to the RS led to a reduction in physician perception of tumour chemosensitivity and strength of ChemoRx recommendation (Table). Use of the RS led to a decrease in Anthracycline (A)-Taxane (T) ChemoRx (30 vs 17 pts) and T-based ChemoRx (30 vs 21 pts) with a resultant increase in non-A, non-T ChemoRx (8 vs 10 pts). The use of the RS did not impact on ChemoRx recommendations in women <40yrs (all got ChemoRx). The biggest reduction in ChemoRx occurred in women age 51-70 with 1LN + (28 vs 18 pts). Overall, in 47 (64%) cases, Oncologists thought the RS significantly changed their treatment recommendations.

Physician questionnaires before and after RS
1. How sensitive will the tumour be to ChemoRx?
12345
Not very sensitiveVery sensitive
Before RS
10 (13)32 (43)21 (28)10 (13)1 (1)
After RS
21 (28)26 (35)15 (20)11 (15)5 (7)
2. How strongly do you recommend ChemoRx?
12345
Not very stronglyVery strongly
Before RS
7 (9)22 (30)20 (27)20 (27)5 (7)
After RS
23 (31)16 (22)10 (13)21 (28)4 (5)

Conclusions

Broader access to the 21 gene RS could result in a reduction in the use of ChemoRx in Ireland.

Legal entity responsible for the study

Cancer Trials Ireland.

Funding

Genomic Health Company.

Disclosure

P.G. Morris: Honoraria: Genomic Health Company. All other authors have declared no conflicts of interest.

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209P - Lymphocyte-predominant breast cancer has a significant lower mean of absolute neutrophil counts compared to non-lymphocyte-predominant breast cancer: Analyses with 576 cases

Presentation Number
209P
Lecture Time
12:45 - 12:45
Speakers
  • Da Young Lee (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Tumor-infiltrating lymphocytes (TILs) in surgical-specimen might be associated with host-cell mediated immunity, which could be partly reflected by blood cell counts from peripheries. We investigated whether peripheral blood cell counts are associated with TILs in 577 patients with breast cancer.

Methods

Between August 2016 and April 2018, we evaluated the percentage of stromal TILs in breast cancer patients who underwent primary surgery according to standardized methodology proposed by the international TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors having high TIL levels (≥ 50%). Blood cell counts including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), percentages of ANC and ALC, and neutrophil-to-lymphocyte ratio (NLR) was obtained from pretreatment laboratory data.

Results

Of 577 tumors, 99 (17.2%) was LPBC, and 478 (82.8%) was non-LBPC. When 5 markers of peripheral blood counts were compared, LPBC had a significantly higher mean ANC than non-LPBC (3,671 vs. 3,336; P = 0.004), but other means were not different. Further, in luminal/HER2-negative breast cancer, mean ANC of LPBC was still higher than that of non-LPBC (P = 0.025), whereas it tended to be higher in LPBC in other subtypes (P = 0.385 in HER2, P = 0.260 in TNBC).

Conclusions

Our results suggest that low peripheral ANC might be linked with LPBC, supporting the hypothesis that systemic immune cell counts might be associated with tumor-immune microenvironment. Further study on an association between peripheral ANC and tumor-associated neutrophil consisting tumor micromileu is warranted.

Legal entity responsible for the study

The Institutional Review Boards of the Gangnam Severance Hospital, Yonsei University, Seoul, Korea.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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210P - Genetic Alterations of Early-Stage Breast Cancers by next-generation sequencing (NGS)

Presentation Number
210P
Lecture Time
12:45 - 12:45
Speakers
  • Yan Xu (Chongqing, CN)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Patients diagnosed with early stage generally have better survival. However, disease free survival differed significantly for different molecular subtypes. Understanding the genetic alterations of early-stage breast cancer may help to identify patients at high risk for relapse.

Methods

We retrospectively reviewed genetic profiling of 53 early-stage breast cancer samples in our institute. Surgical specimens were analyzed using hybridization capture-based NGS ER-seq method, white blood cells as control, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number variation(CNV) of 1021 genes.

Results

Fifty-three surgical specimens from 51 female patients with early-stage breast cancer were analyzed, including two bilateral primary breast cancers with different molecular subtypes. There were 29 HR+/HER2-, 6 HER2+, 6 HR+/HER2+ and 12 TNBC. The median diagnosis age was 43(range 31-67). In addition to TP53, there were 16 genes carried actionable mutations identified (details in table). The most frequently mutant genes were TP53 and PIK3CA, in all molecular subtypes. Among PIK3CA mutations, the H1047R/L were tested in all subtypes. Other gene alterations were highly heterogeneous in different molecular subtypes. HRAS or KRAS mutation was always identified with other genes. For instance, HRAS/PIK3CA and KRAS/AKT1 concurrent in 2 HR+/HER2-, KRAS/PIK3CA concurrent in 1 TNBC. Interestingly, for the two bilateral primary breast cancers, one patient had no overlapping mutation in 2 samples within total 6 variants, the other one only had common HER2 CNV in 2 samples within total 13 variants.

Signaling PathwaysGenetic AlterationsHR+/ HER2-(29)HER2  + (6)HR+/ HER2 + (6)TNBC(12)
p53TP53145411
PI3K/AKT/mTORPIK3CA12313
AKT16---
PTEN3---
NF11---
FLCN1---
Homologous recombination repairBRCA1(gm)---1
BRCA1(sc)-1--
BRCA2(gm)2---
BRCA2(sc)-1--
ATM(gm)--1-
Ras/Raf/MAPKHRAS1---
KRAS1--1
Cell cycleRB11---
CDKN2A1---
CCND11---
RTKsFGFR11-1-
HER2 CNV-45-
EGFR CNV---1

sc, somatic mutation; gm, germline mutation.

Conclusions

Genetic alterations were highly heterogeneous in different molecular subtypes of early-stage breast cancers. And this may contribute to the different relapse risk.

Legal entity responsible for the study

Geneplus-Beijing.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

211P - Oncotype Dx results in patients _40 years, Does age matters?: new insights

Presentation Number
211P
Lecture Time
12:45 - 12:45
Speakers
  • Fernando Namuche (Lima, PE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The 21-gene recurrence score (RS) predicts the benefit of adjuvant chemotherapy (CT) in ER-positive, HER2-negative breast cancer (BC) and has been validated in a population where women under 40 are underrepresented. Young BC pts are more likely to receive adjuvant chemotherapy (CT) in addition to endocrine therapy (ET). Our objective was to assess the RS results in young (≤40 yo) vs older (>40 yo) pts and evaluate the impact of age on clinical decision making according to RS categories.

Methods

We retrospectively reviewed electronic medical files of all patients with early stage hormone receptor BC for whom RS was available between 2007 and 2017 in 3 specialized cancer centers. We used the Mann-Whitney and Chi-squared tests to assess differences between age group. Similarly, we evaluated the association between age groups and treatment, within each ODx category. To determine if age was associated with CT use in the low-risk category, a logistic regression model was constructed.

Results

A total of 551 pts were included, 53 (9.6%) ≤40 yo and 498 (90.4%) >40 yo. No statistical differences were found between the younger and older groups in T (p = 0.874), N (p = 0.794), stage (p = 0.188), or grade (p = 0.791). Young patients underwent radical surgery more frequently than their older counterparts (41.5% vs 25.7%, p = 0.014). Statistically significant differences were also observed in ER mean, which was lower in the younger group (80% vs 90%, p < 0.001). The median RS result was significantly higher in the younger group (19 vs 16, p = 0.009). Also, high-risk recurrence score category was significantly more frequent in the younger group (22.6% vs 9.2%, p = 0.009). In the intermediate-risk category there were no differences in the proportion of patients who received CT according to age groups (p = 0.484). In the low-risk category, 28.0% of patients ≤40 years vs 11.3% of patients >40 years received CT (p = 0.037).

Conclusions

Our results indicate that RS tends to be higher in patients with BC ≤ 40 yo and that the frequency of high-risk RS is significantly higher in the younger group, suggesting biological differences between groups. 28% of young patients with low-risk RS from our cohort are overtreated. Based on these results, it should be considered to develop a test adjusted to the age of the patients.

Legal entity responsible for the study

Oncosalud.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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212P - Impact of BRCA status on outcomes and survival in high-risk early breast cancers

Presentation Number
212P
Lecture Time
12:45 - 12:45
Speakers
  • Elodie Klajer (Besançon, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Relationship between the presence of the BRCA mutation (BReast CAncer) and outcomes is unclear, especially in high-risk breast cancers. The aims were to describe clinical and pathological outcomes considering mutational status and to assess the prognostic impact of germinal BRCA mutated status (BRCAm) in this high-risk population.

Methods

A multi-center retrospective cohort of patients treated in Franche-Comté between 2003 and 2013 for an early breast cancer (eBC) by neoadjuvant and/or adjuvant chemotherapy was analyzed. Clinical and pathological outcomes were described and distributions were compared in regards of mutational status group performing Fisher exact tests. Kaplan-Meier method and log-rank tests were used to compare survival in terms of overall survival (OS. Univariate and multivariate Cox proportional hazards models were estimated for OS.

Results

A total of 2,295 patients were included. Among them, 240 patients were tested (10.5%) including 60 patients diagnosed with BRCAm (2.6%). Among them, 36 were BRCA1 (1.6%), 22 BRCA2 (1%) and two BRCA1 and 2 (0.01%). Age at diagnosis (p < 0.0001), histological type (p = 0.0043), size (p = 0.0021), nodal status (p < 0.0001), histologic grade (p = 0.0009), triple negative status (p < 0.0001) and in situ component (p = 0.0163) were significantly different between BRCAm, BRCAwt and untested patients. BRCA1 mutated tumors were mostly triple negative tumors contrary to BRCA2 mutated tumors, which were mostly locally advanced luminal tumors. In multivariate analysis, OS was not associated with BRCAm status (p = 0.5690).

Conclusions

Among this French cohort of high-risk eBC, incidence of BRACm cases was 2.6%. BRCA1 and BRCA2 breast cancers were two distinct tumors in term of pathological outcomes. BRCAm status had no significant impact on OS.

Legal entity responsible for the study

CHU Besançon.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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213P - Early breast cancer classified as intermediate risk by the Prosigna assay: Characteristics and treatment strategy

Presentation Number
213P
Lecture Time
12:45 - 12:45
Speakers
  • Nawale Hajjaji (Lille, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Genomic-based signatures are implemented in clinical practice to guide adjuvant treatment strategy in early breast cancer patients with luminal tumors. One of the main signatures, the PAM50-based Prosigna assay classifies patients into 3 risk categories based on their score of recurrence, thus providing clear guidance in low or high risk tumors. This study aimed at assessing in real life the proportion of patients with intermediate (ITD) risk results with the Prosigna assay, their tumor profile and the factors influencing treatment decision.

Methods

This monocentric retrospective study was conducted in 107 patients with luminal early-stage breast cancer treated at Oscar Lambret Cancer Center (Lille, France). Their tumors were analyzed with the Prosigna assay from July 2016 through April 2018.

Results

The Prosigna assay classified 15% of the patients in the low risk group, 41% were high risk, and 44% ITD risk. In this group, approximately one third were node negative and two third node positive. The tumor profiles with the highest proportion of ITD risk results had the following characteristics: 14≤Ki67≤20% and grade 2 in node negative or positive patients, or Ki67<14% and grade 2 in node positive patients (Table). 83% of the patients with an ITD risk result (39 of 47) were spared chemotherapy. Among them, 34 had luminal A and 5 luminal B tumors. Among the 8 patients proposed chemotherapy, luminal A and B tumors were evenly split. The main determinant of this decision was an estimated 10-year risk of relapse over 10 or 11%. Table: Prosigna risk groups distribution within patients’ main tumor profiles.

Prosigna risk groups
Low
Intermediate
High
Main Tumor Profiles (99 of 107 patients)n%n%n%Total (n)
14≤Ki67≤20% - G2 - N053374732015
14≤Ki67≤20% - G2 - N10105974117
Ki67<14% – G2 - N066033011010
Ki67<14% – G2 - N10136573520
Ki67>20% – G2 - N021743365012
Ki67>20% – G2 - N1019109111
Ki67>20% – G3 - N0 - T103434577
Ki67<14% – G1 - N12294571147

G: grade; N0/N1: node negative / positive (1 to 3); T1: tumor size ≤ 20mm

Conclusions

Our study showed that a significant proportion of patients were classified in the intermediate risk group, and most were spared chemotherapy. A specific guidance is needed in this risk group.

Legal entity responsible for the study

Centre Oscar Lambret.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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214P - Ki67 as an important predictor for Oncotype Dx Recurrence score risk groups in Early Breast cancer

Presentation Number
214P
Lecture Time
12:45 - 12:45
Speakers
  • Fernando Namuche (Lima, PE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The gene expression profiling assay OncotypeDx (ODx) prognosticates the risk of estrogen receptor positive (ER+) breast cancer (BC) recurrence and assesses the likely benefit from adjuvant chemotherapy in addition to endocrine therapy. There have been several attempts to develop algorithms that provide similar outcome prediction to the ODx assay with the use of routine clinicopathological characteristics. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use.

Methods

We retrospectively reviewed the electronic medical records of 330 patients with early stage ER+ BC for whom ODx recurrence score (RS) was available. Patients were diagnosed and treated at two specialized cancer centers between 2014 and 2017. Our objective was to determine the ki67’s median differences between ODx risk groups. We used Spearman rho for the correlation between Ki67 and ODx score and used Kruskal-Wallis test for compare medians, pairwaise comparison for the intergroup relations.

Results

Mean age at diagnosis was 57.42 years (range 28-89). Mean tumor diameter was 15.67 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. We assessed the correlation between Ki67 and ODx score, with a pearson r:0.31, p < 0.001. The data showed a directly proportional trend between Ki67 and ODx score. Median Ki67 was 20 (1-100). According to ODX RS, 61.5% of tumors were low risk, 30.3% were intermediate risk and, 8.2% were high risk. Median Ki67 within each category group is as follows: low: 15 (IQR:15), intermediate: 20 (IQR:18) and high: 40 (IQR:35), with a statistically significant difference between medians (p < 0.001). In the Pairwise comparison intergroup the data showed: Low-Intermediate (p < 0.05), Low-High (p < 0.001), Intermediate-High (p < 0.001).

Conclusions

The data showed directly proportional trend between Ki67 and ODx score. In our population there is a statistically significant difference between Ki67 medians according to ODx risk groups.

Legal entity responsible for the study

Oncosalud.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

215P - Genetic signatures always suggest undertreatment? Experience with PAM50

Presentation Number
215P
Lecture Time
12:45 - 12:45
Speakers
  • Carolina Sales (Porto, PT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

PAM50 (Prosigna®) identifies a gene-expression profile that categorises early breast cancer (BC) in intrinsic subtypes and gives prognostic estimation based on a 10 year-recurrence risk score (ROR). The purpose of this study was to evaluate the impact of PAM50's information on adjuvant treatment decisions.

Methods

Prospective collection of BC cases treated in a Cancer Centre in the last 10 months, in which PAM50 was used to define treatment strategy. Demographic, clinic and pathologic characteristics are described. Concordance between immunohistochemistry (IHC) and PAM50 subtypes were assessed as well as therapeutic decision changes according to risk stratification, using blind revision. Categorical variables were compared used chi-square test.

Results

Inclusion of 101 patients, median age of 52 years (34-79 years). Fifty-five patients (54.5%) were premenopausal, 71 (70.3%) had ductal carcinomas, 71 (70.3%) pT1c, 99 (98%) G2, 72 (71.3%) pN0, ER positive and HER2 negative. Eighty five(84.2%) had a PR expression above 20% and 63 (62.4%) had a Ki67≤15%. Overall discordance rate between BC subtypes by IHQ and PAM50 was 34%, (p < 0.001). By IHC, 51 (50.5%) were luminal A-like. Forty seven(92%) remained luminal A with PAM 50 [(low ROR: 28 (60%), intermediate:16 (34%), high:3 (6%)]. Four (8%) changed to luminal B [intermediate ROR:1 (25%), high:3 (75%)]. Of the 50 luminal B-like tumours (49.5%), 20 (40%) remained luminal B [intermediate ROR: 8 (40%); high:12 (60%)] and 30 (60%) changed to luminal A [low ROR:18 (60%), intermediate:12 (40%)]. Based on PAM50, adjuvant strategy was changed in 28 patients (28%), (p = 0.001): 15 (54%) changed from endocrine therapy (ET) only to chemotherapy (CT) also and 13 (46%) changed from CT and ET to ET only.

Conclusions

PAM50 availability results in 28% change in adjuvant plan with more cases of chemotherapy. The 34% discordance with classic IHC subgroups, especially in luminal B tumours, underlines the need for more accurate tests in this heterogeneous population to define the adequate adjuvant strategy. A longer follow up is important to evaluate the prognostic value of clinical decisions based on genetic signatures.

Legal entity responsible for the study

Breast Department - IPO-Porto.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

216P - Significance of receptors expression, mitotic index and Ki67 in breast cancer patients with Nottingham Prognostic Index (NPI) poor prognosis score

Presentation Number
216P
Lecture Time
12:45 - 12:45
Speakers
  • Mejri Nesrine (Ariana, TN)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Nottingham Prognostic Index (NPI) is a used prognostic model for breast cancer patients, but new histological prognostic factors are today defined. We evaluated their effect within patients with poor prognosis NPI score.

Methods

We retrospectively selected 351 non-metastatic breast cancer patients with High NPI score (>5,4). They were classified according to surrogate definition of intrinsic subtypes of breast cancer (St Gallen 2015). Several prognostic factors were evaluated. We used log rank test, cox regression model to evaluate the significance of clinic-pathological factors.

Results

Median age of our population was 50 years. They were luminal A in 30%, Luminal B in 43%, HER overexpression in 10% and basal like in 17%. On univariate analysis, menopausal status (HR = 0,32 [0.13-0,76]), endocrine receptors expression (HR = 6,52 [2,57-16,54]), HER2 expression (HR = 3,08 [0.191-10.39]), Mitotic index (HR = 1,05 [1,02-1,09]) and obesity (HR = 3,49 [1,27-9,58]) were significant prognostic factors. There was no prognostic value of age<35 years, Ki 67 cut-off of 20% and nodal capsule rupture. There was a highly significant difference (p < 0.0001) in overall survival between the 4 intrinsic subtypes. Five-year overall survival was 95% for Luminal A, 90% for Luminal B, 56% for HER2 and 36% for basal-like. On multivariate analysis receptors expression and intrinsic subtype were significantly associated to survival (p < 0.05).

Conclusions

In NPI aggressive disease, the most important prognostic factors were receptors expression and intrinsic subtype. The elaboration of a histology-matched NPI score could afford better prognostic evaluation of early stage breast cancer.

Legal entity responsible for the study

Abderrahmen Mami Hospital, Medical Oncology Department.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

217P - Subgroup analyses of efficacy from a phase III study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab in early breast cancer patients

Presentation Number
217P
Lecture Time
12:45 - 12:45
Speakers
  • Javier Cortes Castan (Barcelona, ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

SB3 has been approved by the European Commission as a biosimilar of reference trastuzumab (TRZ). Equivalence for efficacy between SB3 and TRZ based on breast pathologic complete response (bpCR) rates has been demonstrated and previously reported.1 Here we report results of subgroup analyses of efficacy by baseline disease characteristics and demographics.

Methods

Patients received either SB3 or TRZ for 8 cycles concurrently given with chemotherapy (docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide). Then patients underwent surgery followed by 10 cycles of SB3 or TRZ. The primary endpoint was bpCR rate. Subgroup analyses of bpCR rate, total pathologic complete response (tpCR) rate, and overall response rate (ORR) by region, age, ethnicity, hormone receptor status, breast cancer type, and menopausal status was performed.

Results

800 patients (SB3, n = 402; TRZ, n = 398) were included in the per-protocol set (PPS). The bpCR rates were 51.7% for SB3 and 42.0% for TRZ with adjusted difference of 10.70% (95% CI, 4.13, 17.26). Subgroup analysis results are provided in the table. A trend of favourable efficacy of SB3 compared to TRZ was maintained in most of subgroup analyses. Similar trends were observed in the subgroup analysis of tpCR rate and ORR. Table: bpCR rates by baseline demographics and disease characteristics.

SB3 n/n’ (%)TRZ n/n’ (%)Adjusted difference (%) (SB3-TRZ, 95% CI)
Region
Europe53/108 (49.1)44/98 (44.9)3.44 (-9.63, 16.51)
Non-Europe155/294 (52.7)123/300 (41.0)13.18 (5.59, 20.77)
Age
Age <4559/121 (48.8)48/119 (40.3)9.20 (-3.08, 21.48)
Age ≥45149/281 (53.0)119/279 (42.7)11.51 (3.76, 19.26)
Ethnicity
Asian68/124 (54.8)51/124 (41.1)15.52 (4.27, 26.78)
White135/269 (50.2)112/264 (42.4)8.45 (0.28, 16.62)
Hormone receptor status
ER and/or PR positive119/254 (46.9)78/230 (33.9)12.87 (4.45, 21.28)
ER and PR negative89/148 (60.1)89/168 (53.0)7.34 (-3.14, 17.83)
Breast cancer type
Operable120/241 (49.8)97/238 (40.8)10.14 (1.44, 18.85)
Locally advanced88/161 (54.7)70/160 (43.8)11.53 (1.58, 21.48)
Menopausal status
Yes105/198 (53.0)92/198 (46.5)7.65 (-1.33, 16.64)
No103/204 (50.5)75/200 (37.5)12.97 (3.81, 22.14)

CI, confidence interval; ER, oestrogen receptor; PR, progesterone receptor; n, number of patients achieving bpCR; n’, number of patients with available assessment results.

Conclusions

Subgroup analysis results of bpCR, tpCR, and ORR showed a tendency of favourable efficacy in SB3 compared to TRZ, which were consistent with the overall bpCR analysis result. Reference: 1. Pivot X et al. J Clin Oncol. 2018; 36:968-74.

Clinical trial identification

EudraCT: 2013-004172-35.

Legal entity responsible for the study

Samsung Bioepis Co., Ltd.

Funding

Samsung Bioepis Co., Ltd.

Disclosure

J. Cortes Castan: Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer; Consulting/advisor: Roche, Celgene, Aztrazeneca, Cellestia Biotech, Biothera, Merus. X. Pivot: Principle investor: phase III study of SB3; Consultant and honoraria: Samsung Bioepis. G. Curigliano: Fee for a seminar on the abstract. S. Song, Y.C. Yoon: Employment: Samsung Bioepis. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

218P - Autoimmunity and benefit from trastuzumab treatment in breast cancer: results from the HERA phase 3 trial

Presentation Number
218P
Lecture Time
12:45 - 12:45
Speakers
  • Amir Sonnenblick (Tel Aviv, IL)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

A growing body of evidence demonstrates that the immune system contributes to the therapeutic effects of trastuzumab. We sought to determine whether autoimmune background could identify patients with HER2 positive early breast cancer (EBC) who derive differential benefit from adjuvant primary trastuzumab-based therapy.

Methods

HERA (BIG 1-01) is an international, multicenter, open-label, phase 3 randomized trial of 5,102 women with HER2-positive EBC, who were enrolled after completion of their postoperative chemotherapy to receive trastuzumab for 1 year, 2 years, or no trastuzumab. In this exploratory analysis, we evaluated whether there is an interaction between autoimmune history and the magnitude of trastuzumab benefit with respect to disease-free survival (DFS) and overall survival (OS).

Results

A total of 5,099 patients were included in the current analysis: 4,774 patients (93.6%) had no history of autoimmune disease at baseline while 325 patients (6.4%) had autoimmune disease history, 295 of whom had active disease. Median follow-up was 11 years (IQR 10.09–11.53); 1,631 patients experienced a DFS event and 1,037 patients experienced an OS event. Random assignment to 1 or 2 years of trastuzumab compared with no trastuzumab yielded similar reductions in the risk of events for patients with no autoimmune history as for patients with autoimmune history (interaction p = 0.95 for DFS, and p = 0.62 for OS). Trastuzumab reduced the risk of DFS event for both the no autoimmune (HR 0.77, 95% CI 0.69–0.85) as well as the autoimmune history group (HR 0.76, 95% CI 0.51–1.12). The risk of death was also similarly reduced for both groups: no autoimmune history: (HR 0.74, 95% CI 0.65-0.84); autoimmune history: (HR 0.65, 95% CI 0.40-1.07).

Conclusions

We found no evidence of a differential benefit from trastuzumab in patients with a medical history of autoimmune disease.

Legal entity responsible for the study

BrEAST - Amir Sonnenblick.

Funding

HERA was conducted under the umbrella of the Breast international group (BIG), with sponsorship and funding provided by F Hoffmann-La Roche.

Disclosure

C. Jackisch: Advisory board: Roche; Travel grants: Roche. D. Zardavas: Research grants; Roche, Genentech, Pfizer, AstraZeneca. N. Al-Sakaff: Employment: F. Hoffmann-La Roche. R. Gelber: Contributions to clinical trials: Roche, Novartis, Pfizer, AstraZeneca, Ipsen, Ferring, GSK, Celgene. M. Piccart: Consultancy fees: Roche. E. de Azambuja: Research grant, Advisory board and honoraria: Roche; Travel grants: Roche / GSK. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

219P - Impact of hormone receptor status in HER2+ early breast cancer: a paradigm shift in the trastuzumab era

Presentation Number
219P
Lecture Time
12:45 - 12:45
Speakers
  • Alexandre De Nonneville (Marseille, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

While hormone receptor-positive (HR+) and negative (HR-) HER2+ breast cancers (BC) are thought to be distinct diseases, only few studies have investigated the impact of HR status in the context of trastuzumab (TRZ)-treated BC. We evaluated the impact of HR status on outcomes of HER2+ early BC, before and after generalization of TRZ.

Methods

Patients were identified from a cohort of 23,374 women who underwent primary surgery in 18 centers between 2000 and 2017. Since the year 2005 marked the generalization of TRZ, we conducted distinct analyses in patients treated between 2000 and 2004 and those treated between 2005 and 2017. Impact of HR status analyses were done with censorship of events occurring after 5 years in both cohorts. Proportionality tests included all events.

Results

Of 970 HER2+ patients, 349 were treated between 2000 and 2004 without TRZ, and 621 between 2005 and 2017, with TRZ-based adjuvant chemotherapy. Endocrine therapy was received by 92 and 94% of HR+ patients, respectively. In the first group, HR status impacted disease-free survival (DFS) in univariate analysis (Hazard ratio: 2.44 [1.43-4.19]; p < 0.001, log-rank test). Conversely, HR status did not significantly impact DFS in the cohort with TRZ (1.34 [0.66-2.71], p = 0.414). Overall survival was also impacted by HR status in the group without TRZ (Hazard ratio: 2.49 [1.23-5.04]; p = 0.009), but not in the TRZ group (0.68 [0.23-2.00]; p = 0.482). These results were maintained in multivariate analysis including age, LVI, lymph node involvement, histology, grade and tumor size. Evolution of Hazard ratio over time for cumulative incidence of first recurrence according to HR status in patients without TRZ showed a non-proportionality of risks on metastatic (p = 0.027, AD-test) recurrences, with a decreasing risk for HR- over time. Conversely, the analysis of cumulative incidence of first recurrence did not show such a trend in patients treated with TRZ, suggesting the proportionality of the risks over time for HR status.

Conclusions

Instead patients treated without TRZ, HR status was no longer determinant of outcomes when patients received TRZ. These observations are supported by the analysis of Hazard ratio’s evolution over time for cumulative incidence of first metastatic recurrence.

Legal entity responsible for the study

Gilles Houvenaeghel.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

220P - Sefety profile of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: The french HERMIONE non-interventional prospective study

Presentation Number
220P
Lecture Time
12:45 - 12:45
Speakers
  • Jean-philippe P. Jacquin (Saint-etienne, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The HERMIONE study was conducted to assess, in HER2-positive early breast cancer, the safety profile of subcutaneous formulation of trastuzumab (SC T) in real life in France.

Methods

This prospective, multicenter, noninterventional study included 511 patients planned to be treated in both neoadjuvant and adjuvant settings with a follow-up (FU) of 12 months maximum. The safety analyses concerned 505 patients, either naïve (40.4%) or non-naïve (59.6%) of intravenous trastuzumab (IV T). According to routine practice, patients received concomitant locoregional radiotherapy (68.7%), endocrine therapy (59.9%) and chemotherapy (37.8%). Primary endpoint was the description of systemic and local Adverse Events (AEs) of SC T assessed by NCI-CTCAE. Congestive Heart Failure (CHF), hepatobiliary toxicity and suspected transmission of an infectious agent by SC T were AEs of Special Interest (AESIs). Secondary endpoints included description of patients, disease characteristics and modalities of SC T administration. Quality of life (QoL) was assessed by QLQ-C30.

Results

Patients were included in 101 sites between January and November 2015. The median age was 58 years. Over the FU period, AEs occurred in 422 patients (83.6%): 92 AEs (3.8%) were grade ≥ 3, 76 (3.1%) were serious, 87 (3.6%) were AESIs and 336 (13.7%) were related to SC T. Most frequent AEs (> 10% of patients) were asthenia, arthralgia, radiation skin injury, myalgia, hot flush and diarrhea. Main grade ≥3 events were radiation skin injury (1.8% of patients) and febrile neutropenia (1.4%). Serious AEs (SAEs) included febrile neutropenia (9.2% of SAEs) and pulmonary embolism (6.6%). Main AESI was CHF in 11.5% of patients and was related to SC T only in 4.5%. Injection site pain was the main SC Trelated AE (9.1% of patients). Few AEs (1.4%) led to permanent SC T discontinuation. Only 1 death assessed as not related to SC T (pulmonary thromboembolism) was reported. QoL analyses showed no deterioration of global health status.

Conclusions

The Hermione study showed that the safety of SC T (HERCEPTIN®) in a real-life setting is consistent with the known profile, without new safety concerns or QoL deterioration.

Clinical trial identification

NCT02286362.

Legal entity responsible for the study

Hoffmann-La Roche.

Funding

Hoffmann-La Roche.

Editorial Acknowledgement

Stéphanie Mohsen, Aixial.

Disclosure

H. Attar-Rabia, S. Deblay, S. Pibre: Roche employee. Y. Belkacemi: Honoraria and consulting: Astellas, Roche, Genomic Health. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

221P - Real-life data on the cardiac toxicity of adjuvant fixed-dose subcutaneous trastuzumab in HER2-positive breast cancer.

Presentation Number
221P
Lecture Time
12:45 - 12:45
Speakers
  • Rita De Sanctis (Roma, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Fixed-dose adjuvant subcutaneous (s.c.) trastuzumab (T) has been approved in the treatment of early HER2-positive breast cancer (BC), based on the evidence of its non-inferiority to standard intravenous (i.v.) infusion. Few data from real-life are available regarding cardiac toxicities associated with fixed-dose subcutaneous T administration. We conducted a retrospective study in order to compare cardiac toxicity profile of adjuvant fixed-dose s.c.-T and weight-based i.v.-T, according to anthropometric data which takes into account more than simply weight.

Methods

Patients treated with adjuvant T for HER2-positive breast cancer at Humanitas Research Hospital from December 2013 to October 2017 were evaluated. T was administered at a either fixed dose of 600 mg s.c. or 6 mg/kg i.v, respectively. Data regarding previous chemotherapy, Body Mass Index (BMI), and development of cardiotoxicity (decrease in LVEF >10% points, to a value < 50%) were extracted from medical records. Four BMI classes were considered: underweight (BMI < 18 kg/sqm), normal weight (18-24.9 kg/sqm), overweight (25-29.99), and obesity (≥30). All variables were compared with categorical tests (Pearson Chi-squared with Yates correction or Fisher exact test).

Results

A total of 260 HER2-positive BC patients receiving adjuvant T were analyzed. Median age was 56 (range, 32-88), median BMI 23.5 (range, 15.8-50.2 kg/sqm). 196 (75.38%) patients received s.c.-T and 64 (24.62%) i.v.-T. 156 had a normal weight, while 11 were underweight, 54 overweight and 39 obese. The incidence of cardiotoxicity was not different among the BMI classes according to the route of administration of T (p = 0.28). In the subset of the patients who had developed cardiac toxicity, BMI did not result as a risk factor, as well as a previous treatment with anthracyclines (p = 0.89).

Conclusions

Cardiac toxicity profile of fixed-dose s.c.-T is consistent with that of weight-based i.v.-T in the real-world setting regardless differences in anthropometric data as BMI. Our study confirms safety of subcutaneous T administration, which still represents a valid and more convenient alternative to intravenous administration.

Legal entity responsible for the study

Istituto Clinico Humanitas.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

222P - Comprehensive evaluation of the pharmacokinetic profiles of SB3 and reference trastuzumab

Presentation Number
222P
Lecture Time
12:45 - 12:45
Speakers
  • Xavier Pivot (Strasbourg, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

SB3 has been approved by the European Commission as a biosimilar of reference trastuzumab (TRZ). Physicochemical and functional studies showed that SB3 was highly similar to TRZ. Here, the pharmacokinetic (PK) results comparing SB3 and TRZ in cynomolgus monkeys, healthy male subjects, and early breast cancer patients are reported.

Methods

PK profiles were evaluated in cynomolgus monkeys following intravenous administration of 25 mg/kg of SB3 or TRZ every week for 4 weeks. In healthy male subjects, the PK equivalence between SB3 vs. EU-TRZ, between SB3 vs. US-TRZ, and between EU-TRZ vs. US-TRZ were assessed in a Phase I, 6 mg/kg single dose study.1 The trough concentration was evaluated in a Phase III study of early breast cancer patients receiving either SB3 or EU-TRZ in combination with neoadjuvant chemotherapy.2 Equivalence was to be concluded if the 90% confidence interval (CI) for the ratio of geometric lead squares means (LS Means) of the PK parameters were within the standard margins of 80.00% to 125.00%.

Results

Maximum concentration Cmax, time to reach Cmax (Tmax), and the area under the concentration-time curve from time zero to 168 hour (AUC0-168) were similar in cynomolgus monkeys treated with SB3 or TRZ. In 108 healthy subjects, the 90% CIs for the AUC from time zero to infinity (AUCinf), AUC from time zero to the last quantifiable concentration (AUClast) and Cmax for all pairwise comparisons were within the pre-defined equivalence margin. The PK population in Phase III study consisted of 313 patients (SB3, n = 161; TRZ=152). Mean trough concentrations were similar from cycle 3 to 8 of SB3 ranging from 37.71 to 55.80 µg/mL and TRZ ranging from 39.83 to 53.13 µg/mL and the corresponding 90% CIs fell within the pre-defined equivalence margin. The proportion of patients with Ctrough exceeding 20µg/mL was similar between the treatment groups at each cycle.

Conclusions

In addition to the non-clinical study in cynomolgus monkeys, similar PK profiles were well demonstrated between SB3 and TRZ in healthy subjects and in breast cancer patients. Reference 1. Pivot X et al. Clin Ther. 2016; 38:1665-73; 2. Pivot X et al. J Clin Oncol. 2018; 36:968-74.

Clinical trial identification

EudraCT: 2013-004172-35.

Legal entity responsible for the study

Samsung Bioepis Co., Ltd.

Funding

Samsung Bioepis Co., Ltd.

Disclosure

X. Pivot: Principle investigator: Phase III study of SB3; Consultant and honoraria: Samsung Bioepis. S.J. Song, Y.C. Yoon: Employment: Samsung Bioepis. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

223P - The impact of neoadjuvant dual HER2 targeting with Pertuzumab and Trastuzumab on pathological complete response (pCR) rates: Kent Oncology Centre (KOC) experience

Presentation Number
223P
Lecture Time
12:45 - 12:45
Speakers
  • Samantha Forner (Maidstone, GB)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Neoadjuvant chemotherapy (NACT) with dual HER2 targeting improved pCR rates (ypT0ypN0) compared with Herceptin plus chemotherapy in the TRYPHAENA and NeoSphere registration trials. Pertuzumab-containing regimens were adopted at KOC following NICE approval (December 2016).

Methods

A retrospective case notes study of 110 (stage 1-3) HER2+ breast cancer patients receiving HER2-directed NACT at KOC was conducted. Age, clinical stage, ER status, treatment regimen and pCR status were recorded.

Results

Single targeting treatment (S) used FEC-TH. Dual targeting (D) regimens were FEC-THP or TCHP. Patients were well matched for age, clinical stage and ER status. Overall, dual targeting increased pCR rates: 62% vs 31% (S). pCR rates were higher with dual targeting regardless of ER or nodal status. The highest pCR rate was seen amongst ER negative patients receiving D (81%). Amongst D regimens, an excess of ER+ patients was seen in the TCHP group (75% TCHP vs 37% FEC-THP). Despite this, pCR rates were comparable (61% TCHP vs 63% FEC-THP). All 9 ER negative patients treated with TCHP achieved pCR (100%) compared with FEC-THP (67%). Table: Demographics and pCR rates for single and dual HER2 targeted NACT.

Single targeting (S)Dual targeting (D)
Time periodOct 15-Nov 17Dec 16-Nov 17
N5555
Age Median (range)55 (36-78)53 (29-77)
Regimen
FEC-TH55
FEC-THP19
TCHP36
ER status
ER + 31 (56%)34 (62%)
ER -24 (44%)21 (38%)
Node status at diagnosis
N + 37 (67%)29 (53%)
N -18 (33%)26 (47%)
pCR [n (%)]17 (31%)34( 62%)
ER + 11 (35%)17 (50%)
ER -6 (25%)17 (81%)
N + 11 (30%)22 (76%)
N -6 (33%)12 (46%)

Conclusions

A substantial increase in pCR rates was observed with dual targeting, regardless of ER and nodal status, reproducing the registration trial data in real world clinical practice. pCR rates were greatest in ER negative patients, regardless of regimen. The small subgroup most likely to achieve pCR were ER negative patients treated with TCHP.

Legal entity responsible for the study

Kent Oncology Centre, Maidstone Hospital.

Funding

Has not received any funding.

Disclosure

R. Burcombe: Honorarium and advisory board: Roche in 2017 for writing an article (BJN) on HER2 directed therapy for MBC. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

224P - Neoadjuvant Trial of nab-paclitaxel and Atezolizumab (Atezo), a PD-L1 inhibitor, in patients (pts) with chemo-insensitive Triple Negative Breast Cancer (TNBC)

Presentation Number
224P
Lecture Time
12:45 - 12:45
Speakers
  • Jennifer K. Litton (Houston, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Achieving a residual cancer burden (RCB) 0-1 portends an excellent prognosis for TNBC pts receiving neoadjuvant (NACT) anthracycline (AC) and taxane chemotherapy while pts with high residual disease (RCB II-III) have a 40-80% recurrence risk. The GeparTrio and Aberdeen trials demonstrated that pts with poor response by ultrasound (US) during NACT had pathologic complete response (pCR) rates of 2-5% even if NACT was changed based on US response. Immunotherapy is a promising strategy for chemo-insensitive TNBC; however, given toxicity and potential for long-term morbidity, pt selection is important.

Methods

Pts identified as having chemo-insensitive TNBC with AC using US or through previous participation in a separate trial, ARTEMIS, were eligible. To identify insensitive TNBC, ARTEMIS used an algorithm combining a CLIA-certified chemo-sensitivity mRNA gene signature with US response to AC X4. Eligible pts then received weekly nab-paclitaxel (100 mg/m2 IV for 12 weeks) and atezo (1200mg IV q 3 weeks). Atezo continued for 3 months after surgery. Using a 2-stage Gehan-type design, if > 1 pt had an RCB 0-I in the first 19, the protocol would continue to accrue a total of 37 pts to estimate an RCB-0/I rate for atezo + nab-paclitaxel in chemo-insensitive TNBC for future trials. We report the interim analysis of the first 19 pts.

Results

19 pts enrolled from 02/2016- 12/12/2017. One pt received 1 cycle, then withdrew consent. Median age was 54 (range 35-75). Presenting clinical stage was II in 7 pts and III in 12 pts. Final pathology status was: RCB 0=5; RCB I = 1; RCB II = 5 and RCB III=7. RCB 0-I= 6/19 (32%). Toxicity included 6 serious adverse events in 3 pts: fever, elevated creatinine and post-surgical pain. Most common toxicities included fatigue, neuropathy, pain, anemia, rash, elevated transaminases, hyperglycemia, nausea and dyspnea. Six pts required atezo to be held and/or discontinued.

Conclusions

The combination of nab-paclitaxel and atezo resulted in moderate toxicity but increased the expected RCB 0-I rates from 5% to 32% for TNBC patients with chemotherapy-insensitive disease. Given these promising results, this study will continue to full accrual.

Clinical trial identification

NCT02530489.

Legal entity responsible for the study

Jennifer Litton.

Funding

MD Anderson Moonshot Program, Genentech.

Disclosure

J.K. Litton: Advisory boards (without personal compensation): AstraZeneca and Pfizer; Research studies: GSK, EMD Serono, Genentech, Pfizer, AstraZeneca, Novartis; CME with uptodate, med learning group, PER Guidelines; NIH PDQ and NCCN guidelines. E.A. Mittendorf; Advisory board: Merck and Sellas; Principal investigator: Genentech sponsored trials. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

225P - Prognostic implications of circulating tumor cells (CTCs) after neoadjuvant chemotherapy for triple negative breast cancer (TNBC)

Presentation Number
225P
Lecture Time
12:45 - 12:45
Speakers
  • Carolyn Hall (houston, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

ARTEMIS (A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival) is a randomized trial to determine if precision guided neoadjuvant chemotherapy (NACT) impacts rates of pathologic complete response in the breast and axillary nodes (pCR). We hypothesized that CTCs in peripheral blood at the time of surgery, after completion of NACT, would be prognostic in TNBC.

Methods

Venous Blood taken following completion of NACT and immediately prior to surgery was assessed for CTCs after NACT as part of two IRB approved studies, ARTEMIS (2014 – 0185/PA15-1050) and LAB04-0698. CTCs (per 7.5 ml blood) were identified using the Cell Search® System (Menarini Silicon Biosystems). Samples with one or more cells having morphologic criteria for malignancy were deemed CTC+. Log-rank test and Cox regression analysis were applied to evaluate associations between CTC+, pCR, and overall survival.

Results

pCR was achieved in 24/68 (35%) patients with TNBC. Twenty four patients (35%) were CTC+. 3 year overall survival was evaluated in 4 groups of patients: pCR-no CTCs (n = 20), pCR-CTC + (n = 4), non-pCR-no CTCs (n = 24) and non-pCR-CTC + (n = 20). Three year OS was higher in the pCR-no CTCs cohort (100%), compared to pCR-CTC + (50%), non-pCR-no CTCs (83%), non-pCR-CTC + (19%); log rank p < 0.0001. In this data set, the presence of CTCs was associated with significant risk of death at 3 years [hazard ratio of 12.3 (95% CI 3.4-454, p = 0.00002)], whereas a favorable, but non-significant trend was noted for pCR [hazard ratio of 0.2 (95% CI 0.0, 1.4, p = 0.11)].

Conclusions

The presence of CTCs at the time of surgery after NACT has prognostic significance beyond that of pCR and should be considered in evaluation of patients for adjuvant clinical trials.

Legal entity responsible for the study

University of Texas, MD Anderson.

Funding

University of Texas, MD Anderson.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

226P - A prediction model for pathological complete response after neoadjuvant chemotherapy of HER2-negative breast cancer patients

Presentation Number
226P
Lecture Time
12:45 - 12:45
Speakers
  • Lothar Häberle (Erlangen, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Pathological complete response (pCR) is an established surrogate marker for survival in breast cancer (BC) patients treated with neoadjuvant chemotherapy. Prediction of pCR based on clinical information available at biopsy, particularly the biomarkers estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 expression, might assist in the identification of patients who benefit of preoperative chemotherapy. Although biomarker assessment is mostly reported as the percentage of positively stained cells with values from 0 to 100%, cut-off points are used to classify patients into groups. Aim of this study was to examine established cut-off points and to develop a prediction tool estimating a patient’s pCR likelihood obtained from clinical predictors and these biomarkers as assessed during clinical routine or categorically with established or newfound thresholds.

Methods

This study included all HER2-negative BC patients from one German institution treated with neoadjuvant chemotherapy from 2002 to 2017, having complete observations (N = 829). Various logistic regression models for predicting pCR which differ from each other by the usage of the biomarkers were set-up: (M1) continuous biomarkers from 0 to 100% as assessed during clinical routine, (M2) categorical (positive/negative) biomarkers with established thresholds, (M3) categorical biomarkers with newfound thresholds. Prediction accuracy (e.g., AUC) was assessed using cross-validation.

Results

A total of 163 (19.7%) patients achieved a pCR. The optimal cut-off points for ER, PgR and Ki-67 were 30%, 10% and 35%, respectively. The prediction model M1 with continuous biomarkers was more precise (cross-validated AUC, 0.863) than the prediction models M2 and M3 (both 0.854). The most accurate model M1 had a sensitivity of 0.80 at a specificity of 0.78. Beside these biomarkers, a patient’s likelihood of achieving a pCR depended on age at diagnosis, clinical tumor stage and grading.

Conclusions

Using biomarkers as continuous variables yielded more precise predictions than when used categorically. Therapy decisions should base on predicted pCR probabilities obtained from multivariable prediction models rather than single biomarker values.

Legal entity responsible for the study

Erlangen University Hospital, Erlangen.

Funding

Has not received any funding.

Disclosure

A. Hartmann: Personal fees: AstraZeneca, BMS, MSD; Grants: Biontech, Nanostring; Personal fees and non-financial support: Roche, Sysmex; Grants: Janssen, Cepheid outside the submitted work. P.A. Fasching: Grants and personal fees: Novartis; Personal fees: Pfizer, Roche, Teva, Celgene; Grants: Biontech, outside the submitted work. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

227P - Evaluation of the MammaTyper® as a molecular predictor for pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) and outcome in patients with different breast cancer (BC) subtypes

Presentation Number
227P
Lecture Time
12:45 - 12:45
Speakers
  • Peter A. Fasching (Erlangen, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

According to molecular and genetic features BC can be divided into subtypes which show differences in the response to systemic therapy and in long-term outcome. Thus, effective and reliable molecular analysis of tumor material at the time of BC diagnosis is needed.

Methods

Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples of BC patients (pts) enrolled in the single arm phase II TECHNO (Untch et al. JCO 2011) and the randomised phase III PREPARE (Untch et al. Ann Oncol. 2011) trials. MammaTyper®, a molecular in vitro diagnostic RT-qPCR test, was used to assess the expression of ERBB2 (HER2), ESR1 (ER), PGR (PR) and MKI67 (Ki67) genes as continuous and binary variables using predefined cutoffs. Pts were classified into 6 intrinsic BC subtypes according to St Gallen guidelines (Goldhirsch et al. Ann Oncol. 2013). In both trials the ER, PR, HER2 and Ki67 expression was assessed by immunohistochemistry (IHC). Predefined cutoffs for increased ESR1 (+1.8 Cq) and PGR (+3.7 Cq) expression defined a subgroup of ultra-high tumors. The study aimed to evaluate the MammaTyper® test for predicting pCR (ypT0 ypN0) after NACT and outcome in the BC subtypes. The degree of agreement between the MammaTyper® and the IHC test for determining BC subtypes was also estimated.

Results

A total of 418 pts were assessed. The BC subtypes defined by MammaTyper® and IHC showed good agreements (ERBB2/HER2, kappa [κ]=0.674; ESR1/ER, κ = 0.815; PGR/PR, κ = 0.648). MKI67 significantly predicted pCR (AUC=0.686, p < 0.001). In HER2+ pts from the TECHNO trial the ERBB2 significantly predicted pCR in ESR1-positive sybtype (n = 59, AUC=0.708, p = 0.006). HER2-negative pts from the PREPARE trial with ultra-high ESR1 and/or PGR expression had significantly better disease-free (DFS) and overall survival (OS) than the non-ultra-high pts (n = 153; DFS HR = 1.80, [95%CI 1.18-2.76], p = 0.007; OS HR = 2.54 [95%-CI 1.50-4.31], p = 0.001).

Conclusions

The MammaTyper® significantly predicts response after NACT in BC subtypes. A subgroup of pts with ultra-high ESR1/PGR expression had a good prognosis. Further analysis is required.

Legal entity responsible for the study

GBG Forschungs GmbH and BioNTech Diagnostics GmbH.

Funding

This study was financially supported by BioNTech Diagnostics GmbH, Mainz, Germany.

Disclosure

P.A. Fasching: Grants: Biontech, during the conduct of the study; Grants and personal fees: Novartis; Personal fees: Pfizer, Roche, Teva, Celgene, outside the submitted work. M. Laible: Patent WO 2015/024942, Commercialized as MammaTyper(TM) Kit; Relevant financial activities outside the submitted work: BioNTech Diagnostics GmbH (Employee of BioNTech Diagnostics GmbH). K.E. Weber: Grants and non-financial support: BioNTech Diagnostics GmbH, Mainz, Germany, during the conduct of the study; Patent EndoPredict issued. C. Denkert: Personal fees: Teva, Novartis, Pfizer, Roche, Amgen, MSD Oncology; Other: Sividon Diagnostics, outside the submitted work. K. Schlombs: Personal fees: BioNTech Diagnostics GmbH, outside the submitted work; Patent WO 2015/024942 pending; New Patent application pending. F. Marme: Personal fees: Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, GenomicHealth, CureVac, Eisai, outside the submitted work. S. Loibl: Grants: AbbVie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Teva, Vifor during the conduct of the study and outside the submitted work. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

228P - Impact of clinical, morphologic and molecular characteristics on response to neoadjuvant systemic therapy (NAST) in metaplastic breast cancer (MpBC)

Presentation Number
228P
Lecture Time
12:45 - 12:45
Speakers
  • Clinton Yam (Houston, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

MpBCs are morphologically heterogeneous, frequently triple-negative and resistant to chemotherapy. To better understand why MpBCs are resistant to chemotherapy, we investigated associations between response to NAST and clinical, morphologic, as well as molecular characteristics in a cohort of MpBC patients (pts).

Methods

19 MpBC pts were identified from a prospective cohort of 242 triple-negative breast cancer (TNBC) pts treated with anthracycline-based NAST. Histologic subtype of MpBC was determined by light microscopy. TNBC subtypes were determined using the Vanderbilt gene expression signatures (GES). Residual cancer burden (RCB) was assessed after surgery.

Results

Of the 19 MpBCs, 37% (7/19) were matrix producing and 63% (12/19) were not. Analysis of GES revealed the following subtype distributions: mesenchymal (M)=32% (6/19), mesenchymal stem-like (MSL)=11% (2/19), basal-like 2 (BL2)=32% (6/19), immunomodulatory (IM)=11% (2/19), unstable (UNS)=11% (2/19), basal-like 1 (BL1)=5% (1/19). Fifty-seven percent (4/7) and 33% (4/12) of the matrix producing and non-matrix producing MpBCs were of the M/MSL subtype, respectively. Twenty-one percent (4/19) of pts had a pathologic complete response (pCR)/minimal residual disease (RCB-I) following NAST. MpBCs that were matrix producing or of the M/MSL subtype were associated with worse response to NAST as none (0/11) of the pts with MpBC that was matrix producing and/or of the M/MSL subtype had a pCR/RCB-I, compared with 50% (4/8) of the remaining pts (p = 0.018).

Associations between response to NAST and clinical, morphological as well as molecular characteristics

pCR/RCB-I (n = 4)RCB-II/III (n = 15)
Median age (range)57.3 (42.4-67.2)57.8 (34.2-74.0)
Mean tumor size - cm (SD)2.4 (1.2)4.7 (3.8)
Clinical nodal status
Negative - n (%)4 (25)12 (75)
Positive - n (%)03 (100)
Stage
I - n (%)2 (40)3 (60)
II - n (%)2 (20)8 (80)
III - n (%)04 (100)
Histologic grade
1 - n (%)01 (100)
2 - n (%)1 (25)3 (75)
3 - n (%)3 (21)11 (79)
Metaplastic subtype
Matrix producing - n (%)07 (100)
Non-matrix producing - n (%)4 (33)8 (67)
TNBC subtype
M/MSL - n (%)08 (100)
BL1/2 - n (%)3 (43)4 (57)
Other - n (%)1 (25)3 (75)

Conclusions

Analysis of GES suggest that MpBC is enriched for subtypes less likely to achieve pCR/RCB-I with NAST (BL2, M, MSL). Matrix-producing (light microscopy) and the M/MSL subtypes (GES) appear to be associated with resistance to anthracycline-based NAST in MpBC.

Legal entity responsible for the study

The University of Texas MD Anderson Cancer Center.

Funding

National Comprehensive Cancer Network (NCCN) Oncology Research Program, The MD Anderson Cancer Center Moonshots Program, CPRIT Multi-Investigator Research Award (MIRA).

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

229P - Evaluation of Human epidermal growth factor receptor 2 overexpression (HER2+) after administration of neoadjuvant treatment (NAT) and prognostic impact in breast cancer (BC)

Presentation Number
229P
Lecture Time
12:45 - 12:45
Speakers
  • Duarte H. Machado (Lisbon, PT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

HER2+ occurs in 15-20% of BC and is associated with worse prognosis. While previous studies reported that NAT-associated changes in HER2 status adversely affect patients (pts) prognosis (Guarneri et al), others did not (Yoshida et al). To assess the efficacy of NAT in pts with HER2+ BC and its influence on HER2 status and associated prognostic impact. HER2 status was determined by immunohistochemically (IHC) or Silver in situ hybridization (SISH).

Methods

Retrospective chart review and pathologic evaluation of all consecutive pts with HER2+ BC (defined as IHC 3+ or IHC 2+ confirmed by SISH) submitted to NAT between Jan2010 and Oct2015 in 3 Portuguese Hospitals. All diagnostic tumor biopsies and surgical specimens were assessed for IHC.

Results

108 female pts were included (median age 52yo, range 30-82; TNM stage was III in 68, II in 40. Hormone receptor (HR) were positive (ER and/or PR) in 68. HER2 status at diagnosis was IHC 3+ in 100 pts and IHC 2+ SISH amplified in 8. NAT included chemotherapy (CT) in all pts (anthracyclines (AC)/ taxanes (Tax) 102, AC/non-Tax 3, non-AC regimen 3), trastuzumab (T) in 87 and T and pertuzumab (P) in 3. Pathological complete response (pCR) (ypT0/isN0) was achieved in 48 pts (44.4%): 28 of 70 HR+ and 20 of 38 HR neg (p = 0.2), 27 of 40 with stage II and 21 of 68 with stage III (p < 0.001). pCR rate was 46% after CT+T/P and 39% with CT alone (p = 0.6). With a median follow-up of 55 months, there were 5 disease free survival (DFS) events (4 relapses and 1 non-BC death) among pCR pts and 19 among non-pCR (16 relapses and 3 non-BC deaths) (p = 0.02, log rank test). Of the 60 pts with residual invasive tumor at surgery, 52 remained HER2+ and 8 (13.3%) lost Her2+. 5y-DFS and 5-OS is 70% and 84%, respectively, for pts whose tumors remained HER2 + (14 DFS events; 8 deaths), and 21% and 50% for pts whose residual tumors became HER2 negative (5 DFS events; 4 deaths) (p = 0.02 and <0,001, log-rank test).

Conclusions

We confirmed the negative prognostic impact of NAT-induced HER2 loss on residual tumor leading to worse DFS. Despite the retrospective design and small sample size, these results suggest the importance of retesting HER2 after NAT, to better refine pts prognosis.

Legal entity responsible for the study

José Luís Passos Coelho.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

230P - Complete response (CR) to anthracycline-based chemotherapy using magnetic resonance imaging (MRI) predicts high rates of pathologic complete response (pCR) for triple negative breast cancer (TNBC) patients treated preoperatively with anthracycline and taxane-based regimens

Presentation Number
230P
Lecture Time
12:45 - 12:45
Speakers
  • Maria Marin Alcala (Sabadell, ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Predictors of pCR to neoadjuvant chemotherapy (NAC) for breast cancers have been studied extensively. We focused on CR to antracycline-based chemotherapy using MRI for prediction of pCR, in patients treated with NAC with anthracycline and taxane-based regimens.

Methods

Tumor measurements were done at diagnosis, after anthracyclines and at the end of taxanes. pCR was defined as absence of residual invasive foci and no lymph nodeinvolvement. Associations of clinicopathologic parameters with pCR were evaluated with the χ2 test. All test results with a p value of less than 0.05 were considered significant.

Results

A total of 114 TNBC patients were treated with NAC. Median age was 53 (28-77) years. 44 patients (38.6%)had stage II and 67(58.8%)stage III. Mutation in BRCA was detected in 9 patients and variants of uncertain significance in 5. 49 patients (43%) with tumor size by MRI > 50 mm, 49 (43%) with positive results on fine needle aspiration of axilla (FNAA), and 88 (77.2%) with histologic grade III. NAC regimen consisted in 108 patients (94.7%) of 4 cycles of epirrubicin+cyclophosphamide (CP) and in 3 patients (2.6%) 4 cycles of doxorubicin+CP, followed by taxane-based regimens. 43 patients (37.7%) had pCR. CR by MRI occurred in 22 patients (19.3%) after anthracycline-based regimen. At the end of NAC there were 37 patients (32.5%) with CR by MRI. Association of clinicopathologic parameters with pCR were: 62.8% pCR in patients with tumor size ≤ 50mm (p = 0.389); 58.1% in patients with FNAA + (p = 0.238); 81.4% in grade III tumors (p = 0.700); 46.5% pCR in patients with CR by MRI after anthracycline-based regimen (p = 0.0001) and 65.1% pCR in patients with CR by MRI before surgery (p = 0.0001). All the patients with CR by MRI after anthracycline-based regimen had a CR by MRI before surgery.

Conclusions

CR by MRI after treatment with anthracyclines could be a clinically useful predictor of pCR in patients with TBNC treated preoperatively with anthracylcines and taxane-based regimens and patients who not reach CR after anthraclines could benefit from improve taxans regimen.

Legal entity responsible for the study

Luis Antonio Fernandez Morales.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

231P - Immunomonitoring of triple negative breast cancer patients undergoing neoadjuvant therapy (GBG89, Geparnuevo trial)

Presentation Number
231P
Lecture Time
12:45 - 12:45
Speakers
  • Barbara Seliger (Halle, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The Geparnuevo trial is a randomized, double-blind, multi-center phase II trial of neoadjuvant therapy in patients with early-stage triple negative breast cancer (TNBC) investigating the role of durvalumab, an anti-PD-L1 inhibitor in addition to standard chemotherapy with nab-paclitaxel followed by epirubicin plus cyclophosphamide.

Methods

In order to determine possible predictive and / or prognostic biomarkers, blood samples were taken before and during the different treatment phases and evaluated by multicolor flow cytometry.

Results

Evaluation of the absolute cell count in the whole blood highlighted a mixed behavior of the total leukocytes, whereas there was a statistically significant reduction in the lymphocytes, particularly during the last phase of the treatment. Further dissection into the different immune populations highlighted an almost complete loss of B cells that in some patients was also accompanied by a reduction of NK cells, mostly regarding the CD16+ subset. However, the loss of CD4+ and CD8+ T cells has been less pronounced resulting in an overall enhancement of their percentages within the total lymphocytes. The different populations have also been evaluated for the expression of activation and exhaustion markers, whose behavior will be more deeply evaluated when the clinical outcome and the treatment received by the various patients will be made available.

Conclusions

We expect that with such analysis possible biomarkers for the treatment of TNBC patients will be identified thus leading to better patient selection for chemo/immune combination therapy.

Legal entity responsible for the study

GBG.

Funding

AstraZeneca and Celgene.

Disclosure

The author has declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

233P - Impact of breast cancer subtype on survival after lumpectomy versus mastectomy for early stage invasive breast cancer

Presentation Number
233P
Lecture Time
12:45 - 12:45
Speakers
  • YU-CHEN Tsai (Taipei, TW)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Randomized clinical trials (RCT) have demonstrated equivalent survival for breast-conserving therapy with radiation (BCT) and mastectomy for early-stage breast cancer. Early stage breast cancer patients who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in a single institution series, and whether survival differed by surgery type when stratified by breast cancer subtypes.

Methods

Information was obtained from the institutional breast cancer data base with stage I or II breast cancer between 1990 and 2010, who were treated with either BCT or mastectomy and followed for vital status through December 2014. Cox proportional hazards modeling was used to compare overall survival (OS) and disease-specific survival (DSS) between BCT and mastectomy groups. Analyses were stratified by breast cancer subtype.

Results

A total of 3486 women fulfilled eligibility criteria. Women undergoing BCT had improved OS and DSS compared with women with mastectomy (adjusted hazard ratio for OS = 0.69, 95% CI = 0.51-0.95, p = 0.0.023; adjusted hazard ratio for DSS =0.68, 95%CI =0.48 -0.96, p = 0.029). 10 year overall survival rate in women undergoing BCT was 95.2% in Luminal A, 94.8% in Luminal B, 84.8% in Luminal/HER2, 91.5% in HER2 enriched and 92.1% in Triple negative. 10 year overall survival rate in women with mastectomy was 91.2% in Luminal A, 82.3% in Luminal B, 89.5% in Luminal/HER2, 86.2% in HER2 enriched and 88.4% in Triple negative.The group achieving greatest benefit in OS and DSS with BCT relative to mastectomy were stage II luminal B patients (adjusted hazard ratio for OS = 0.28, 95% CI = 0.1-0.82, p = 0.02; adjusted hazard ratio for DSS =0.31, 95%CI =0.11 -0.91, p = 0.0329).

Conclusions

Among patients with early stage breast cancer, BCT was associated with improved DSS and OS. These data provide confidence that BCT remains an effective alternative to mastectomy for early stage disease. The group achieving greatest benefit in DSS and OS with BCT relative to mastectomy were stage II Luminal B patients.

Legal entity responsible for the study

Koo Foundation Sun Yat-sen Cancer Center, Taipei, Taiwan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

234P - Survival Outcomes of Dose Dense Neoadjuvant and Adjuvant Chemotherapy in Triple-Negative Breast Cancer Patients – Indian Scenario

Presentation Number
234P
Lecture Time
12:45 - 12:45
Speakers
  • TANVI Sood (Bangalore, IN)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Breast cancer is the most common cancer in Indian women. Triple negative breast cancer (TNBC) is associated with poor prognosis at any stage of diagnosis. It is an aggressive disease with a 5-year survival rate of 77% compared to 93% for other subtypes. Prevalence of TNBC in India is higher compared to western populations, making it an important target for early detection and treatment. Potential superiority of dose-dense chemotherapy in comparison with conventional regimen has been recently demonstrated in a meta-analysis in 2017 across various subsets of breast cancer. Aim of this study was to analyse survival outcomes in TNBC treated with dose dense chemotherapy at a tertiary care centre in India.

Methods

Retrospective analysis of patients diagnosed with TNBC stage I-III in last 8 years treated with 2 weekly dose dense AC regimen (adriamycin at 60mg/m2and cyclophosphamide at 600mg/m2 for 4 cycles followed by 2 weekly Paclitaxel at175 mg/m2 for 4 cycles or weekly Paclitaxel at 80 mg/m2 for 12 cycles) with growth factor support in adjuvant or neoadjuvant (NACT) setting. Locally advanced breast cancer (LABC) was defined as T > 5cm and ≥N2 disease. Kaplan–Meier method and log rank test were used to estimate survival functions.

Results

97 patients with ER, PR and Her2neu receptor negative status were evaluated. Median age at diagnosis was 44 years (range 26 - 68 years). 56.7% had stage II disease, 36% stage III and rest stage I (7.2%). Disease free survival (DFS) rate ± SE at 2 years and 5 years was 90% ± 3% and 75% ± 5% respectively. Overall survival (OS) rate ± SE at 5 years was 82% ± 6%. 24 patients received NACT out of which 12 (50%) patients had pathCR. The DFS rate did not differ significantly between adjuvant and neoadjuvant subgroups. Early breast cancer and LABC subgroups had a statistically significant difference in DFS rates (p = 0.0002).

Conclusions

To our knowledge, this is the first study in India to evaluate survival outcomes of dose dense therapy in TNBC. The improved DFS (75%) and OS (82%) in this high risk subgroup are very promising, especially in patients with early disease. We advocate use of dose dense regimen in all patients of TNBC in curative setting.

Legal entity responsible for the study

Manipal Hospital Ethics Committee.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

235P - Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 and molecular subtype.

Presentation Number
235P
Lecture Time
12:45 - 12:45
Speakers
  • Bernardo L. Rapoport (Sandton, ZA)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in patients (pts) undergoing endocrine treatment for breast BC. The role of Ki-67 in pts undergoing neoadjuvant chemotherapy (NAC) for early BC remains controversial.

Methods

We analyzed retrospectively data on 137 patients undergoing taxane and/or anthracycline, transtuzumab based NAC. Luminal A was documented in 6 pts, Luminal B in 29 pts, Her-2 positive in 30 pts and triple negative breast cancers (TNBC) in 72 pts. Pathological complete response (pCR) was defined as the complete disappearance of the invasive cancer in the breast and absence of tumor in the axillary lymph nodes examined by axillary clearance.

Results

The pCR rate of the entire cohort was 41.6%. At 2 years 92% of pts who attained a pCR were disease free compared to 80% of pts who did not attain a pCR (log rank test p < 0.0147). On univariate analysis factors associated with higher pCR included primary tumor size (T1 68% vs. T2 41% vs. T3 or T4 0%, Chi2=20.05, p < 0.00017), nodal disease (N0 49% vs. N1 39% vs. N2 8%, p < 0.02948), ER receptor status (negative 59% vs. positive 14%, p < 0.00000), PR receptor status (negative 53% vs. positive 17%, p < 0.00002), molecular subtype (TNBC 53.4%, Her2=50% and Luminal A + B was 8.5%, p < 0.00002), Ki67 (>40=55% vs. 15-39=34% vs. <15=0%, p < 0.00060) and Stage (I = 85% vs. IIA=49% vs. IIB=36% vs. III=5%, p < 0.00006). Factors not associated with a higher pCR included age, menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p < 0.01203) and molecular subtype (p < 0.02228) retained its significance; while tumor size, stage of disease, nodal status, ER and PR loss significance.

Conclusions

Ki67 and molecular subtype (Her-2 positive disease and TNBC) are independent prognostic factors of pCR in pts with early BC undergoing NAC.

Legal entity responsible for the study

The Medical Oncology Centre of Rosebank.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

236P - The accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy in clinically node positive breast cancer patients: A single institution experience

Presentation Number
236P
Lecture Time
12:45 - 12:45
Speakers
  • Narges Sistany Allahabadi (Tehran, IR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Sentinel lymph node dissection (SLND) after neoadjuvant chemotherapy (NAC) is of questionable accuracy. In this study we evaluated the feasibility and accuracy of SLND in breast cancer patients with clinically positive axillary nodes.

Methods

We conducted a prospective cross-sectional study on breast cancer patients diagnosed at Milad Hospital of Tehran, Iran from June 2014 to February 2015. Biopsy-proven node positive patients who converted to clinically node-negative following NAC and had a successful SLND (more than three identified SLNs) were included in the study. We used a 2 × 2 contingency table to analyze the feasibility of SLNB (sensitivity, specificity, false negative ratio, and accuracy). STATA statistical software (version 13.0, StataCorp LP, Texas, USA) was used for statistical analysis.

Results

Among 52 patients who entered the study, 47 had a successful SLND (more than three identified SLNs) in whom we achieved a sensitivity of 100% (16/16), false-negative rate of 0% (0/21), a negative predictive value of 100% (16/16), and an overall accuracy of 89.4%.

Conclusions

SLND seems to be feasible and accurate in clinically lymph node positive breast cancer patients who achieve a clinically negative node status following neoadjuvant chemotherapy.

Legal entity responsible for the study

Iran University of Medical Sciences.

Funding

Milad General Hospital - Iran National Social Security Organization.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

237P - Index BRCA1/2 testing under a multidisciplinary program

Presentation Number
237P
Lecture Time
12:45 - 12:45
Speakers
  • Duarte H. Machado (Lisbon, PT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Germline BRCA1/2 mutations are the main cause of Hereditary Breast and Ovarian Cancer syndrome (HBOC). Whenever possible, Index testing should be done in a family member with a previous breast or ovarian cancer (affected individuals, AI) and not in non-affected individuals (NAI). In here we review the characteristics, decisional process and BRCA1/2 mutation detection rate of index testing in AI and NAI.

Methods

Analysis of all consecutive HBOC files registered from November 2000-December 2017. The BRCAPRO model was applied to affected patients (pts) and the Tyrer-Cuzick model to all non-affected female individuals. Comprehensive BRCA1/2 analysis was done, including MLPA and c.156_157insAlu testing (Machado PM et al., 2007)

Results

6112 individuals were counseled and 4642 (76%) consented on genetic BRCA1/2 testing: 3420 (56%) index pts and 1222 (20%) family relatives. Index pts: 3361 (98.3%) had a previous cancer diagnosis (AI) and 59 were NAI. Both groups included mostly women (AI-95.2%; NAI-97%). The mean age for NAI was 40.7 years (20-79) and 79% had at least one-first degree relative with breast or ovarian cancer. Testing decision for NAI: either affected relatives were dead (80%), refused testing (15%) or were unreachable (5%). The global BRCA1/2 detection rate for index pts was 10.44%, being higher (13.6%) for NAI index cases (8 pathogenic variants: 2 BRCA1, 6 BRCA2). The mean pretest BRCA mutation probability (P) for NAI was 10.72% (range 0.06-42.8). This P was 18,5% for those who tested positive and 9,45% for inconclusive results ( p > 0.05). The pre-test lifetime breast cancer risk was 26.69% for all NA cases, being higher for those found to be BRCA1/2 carriers (36.07% vs 28.04%).

Conclusions

Our conservative approach allowed for a detection rate in NAI that compared favorably to affected index pts. Although some groups propose widespread BRCA1/2 screening we suggest that NAI should be tested as index only if no cancer relatives are available. Despite the small sample size, the BRCA pre-test probability of 10% or higher seems to increase the detection rate in this subgroup.

Legal entity responsible for the study

Fátima Vaz.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

238P - BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients

Presentation Number
238P
Lecture Time
12:45 - 12:45
Speakers
  • Alex Friedlaender (Geneva, CH)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

BRCA1 and BRCA2 proteins play a central role in DNA repair process. We hypothesize that BRCA1/BRCA2 germline mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy.

Methods

We included women with primary breast cancers treated with (neo)adjuvant chemotherapy and screened for BRCA1/BRCA2 germline mutations in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3-4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use, and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort).

Results

Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA2 carriers. None of the patients received dose-dense (every 14 days) chemotherapy. Following the C1, febrile neutropenia had an incidence of 35% (p = 0.002), 14% (p = 0.562) and 10% among BRCA1, BRCA2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 (p < 0.001), 14% of BRCA2 (p = 0.861) and 18% of non-carriers. G-CSF support was necessary in 86% of BRCA1 (p = 0.005), 64% of BRCA2 (p = 0.285) and 51% of non-carriers. Among patients with triple-negative breast cancers, febrile neutropenia (35% vs. 12%, p = 0.038), grade 3-4 neutropenia (73% vs. 28%, p = 0.003) and grade 4 neutropenia (60% vs. 13%, p = 0.001) were significantly more frequent in BRCA1 carriers compared to non-carriers. Among BRCA1 carriers, the majority of patients were likely to have grade 3-4 neutropenia (88%; p < 0.001), but none of those having mutations located in the RING domain (0%, p = 0.165) compared to non-carriers. For long-term toxicity analysis, 898 patients were included (167 BRCA1-, 91 BRCA2- and 640 non-carriers). There was no difference between the three groups.

Conclusions

BRCA1 germline mutations predispose breast cancer patients to greater acute hematological toxicity. This has implication for primary prophylaxis with G-CSF.

Legal entity responsible for the study

Intidhar Labidi-Galy.

Funding

La Fondation Henriette Meyer.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

239P - PALB2 germ-line mutations in Russian breast cancer patients: identification of recurrent alleles and analysis of phenotypic characteristics of the tumors

Presentation Number
239P
Lecture Time
12:45 - 12:45
Speakers
  • Evgeny N. Imyanitov (Saint-Petersburg, RU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

PALB2 is a well-known gene for hereditary breast cancer (BC). However, PALB2-driven BCs are less studied as compared to BRCA1/2-related malignancies, due to rarity of PALB2 deleterious alleles.

Methods

PALB2 germ-line mutation analysis was performed using blood-derived DNA.

Results

Sequencing of the entire coding region of PALB2 gene in 190 BC patients, who had evident clinical features of hereditary disease, but lacked BRCA1/2 germ-line mutations, led to the identification of 5 PALB2 mutation carriers. In addition, we considered 4 PALB2 heterozygotes, which were identified in our earlier study [Sokolenko et al., 2015]. The mutation spectrum was represented by 7 distinct pathogenic alleles (с.1317delG, c.172-175delTTGT, c.509-510delGA, R414X (n = 2), Q921X, c.1592delT and Y1055X (n = 2)). These 7 mutations were further screened in 1126 consecutive BC cases. This analysis revealed 8 additional instances of PALB2 mutations (c.509-510delGA (n = 5), c.172-175delTTGT (n = 2), c.1592delT (n = 1)). None of the above mutations was detected in 638 elderly tumor-free controls. Among 18 patients with PALB2-related BC, only 8 women were younger than 50 years; 6 patients reported family history of BC disease and 4 suffered from bilateral BC. IHC data were available for 10 tumors: 1 case was triple-negative, 1 BC demonstrated HER2 activation coupled with negative staining for hormone receptors (HR), and the remaining 8 cases were HR+. Loss-of-heterozygosity (LOH) analysis of 8 chemonaive BCs revealed somatic deletion of the remaining PALB2 allele in 5 tumors and retention of heterozygosity in 3 cases. In addition, we analysed 2 residual BC samples obtained after neoadjuvant therapy and revealed the intact PALB2 wild-type allele in both cases.

Conclusions

PALB2 germ-line mutations contribute to a fraction of BC morbidity in Russia, with PALB2 c.509-510delGA allele being the most frequent pathogenic variant. Interpatient variability with regard to somatic inactivation of the wild-type PALB2 allele deserves attention, given that intratumoral PALB2 status is likely to influence the drug sensitivity of BC.

Legal entity responsible for the study

N.N. Petrov Institute of Oncology.

Funding

Russian Science Foundation.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

240P - Landscape of germline mutations in hereditary breast and ovarian cancer (HBOC) patients in Russia revealed by target panel sequencing

Presentation Number
240P
Lecture Time
12:45 - 12:45
Speakers
  • Elena Shagimardanova (Kazan, RU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Hereditary breast and ovarian cancer (HBOC) is one of the most frequent disorders among other cancers, caused by presence of germline pathogenic variants in patients. Awareness about presence of actionable mutations (BRCA1,2, ATM and others) is beneficial for patients with breast and ovarian cancer due to possibility of targeted treatment, monitoring risk groups among healthy carries and other aspects. In this study we reveal and characterize pathogenic germline mutations in HBOC patients from different regions in Russian Federation.

Methods

Individuals with “family history” were chosen to be included in this study according to the following criteria: (1) young age of disease onset, (2) the presence of relatives with breast or ovarian cancer diagnosis. Information about nationality, age at diagnosis, family cancer history, estrogen, progesterone and Her2 receptor status was collected. The NimbleGen SeqCap EZ Choice kit (“Roche”) was used for target enrichment, and sequencing was performed using Illumina MiSeq (“Illumina”) using paired-end 2 × 251 nucleotide single-index sequencing. HGMD Professional 2017.4 and BIC databases were used to identify pathogenic mutations.

Results

568 patients with breast or ovarian cancer aged from 21 to 82 years old were included in this study. 103 woman has their first cancer diagnosis before 40 years old, 305 – between 40 and 60 years old, 160 - were older than 60. 193 patients had first degree kinship relatives suffered from HBOC syndrome and 165 patients had relatives with other cancers. Of the 568 patients, 22,5% (128) carried pathogenic or likely pathogenic mutation in BRCA1 gene, 9,2% (52) in BRCA2 gene, 17,6% (100) in one of other HBOC related genes, including CDK12, ATM, CDH1, APC, FANCI, CHEK2, FANCL, BARD1, RAD51C, MUTYH, RAD51D, PALB2, FANCA, XRCC2, RAD54L, CHEK1.

Conclusions

Among patients with fulfilling NCCN criteria of hereditary breast or ovarian cancer, only 30% of cases might be explained by BRCA1 or BRCA2 mutation. Panel sequencing is powerful strategy to find variants in other genes, which may play a role in cancer development. It has to be noted that many variants in non-BRCA genes were identified is of unknown significance (VUS) due to absence of database with common variants for Russian population.

Legal entity responsible for the study

Tatarstan Cancer Center.

Funding

The work is supported by the Russian Foundation for Basic Research № 18-415-160009 r_a and according to the Russian Government Program of Competitive Growth of Kazan Federal University.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

241P - Lynch syndrome-associated hereditary mutations cause breast and ovarian cancer: results from Russian Heredetary Oncogenomics project

Presentation Number
241P
Lecture Time
12:45 - 12:45
Speakers
  • Marat Gordiev (Kazan, RU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Lynch syndrome is a hereditary disease caused by mutations in DNA mismatch repair system (MMR), which includes ML1, MS2, MS6, PMS2, EPCAM genes. Clinical manifestation of the Lynch syndrome is usually colorectal cancer (CRC), endometrial cancer, ureteral cancer and kidney cancer. We aimed to analyze occurrence of mutations in MMR system genes in patients with hereditary breast and ovarian cancer.

Methods

We have analyzed 228 samples of blood from patients with hereditary breast (BC) and ovarian cancer (OC) in Tatarstan Regional Clinical Cancer Center, Russia. The criteria for inclusion was at least one out of three observations: Young age of manifestation of breast or ovarian cancer (before 50 y.o. for BC and 55 y.o. for OC), first or second-degree relatives with breast or ovarian cancer, primary-multiple BC and OC. The libraries for sequencing were prepared using NimblGen SepCapEZ Choice (Roche) with custom gene panel followed by sequencing on MiSeq platform.

Results

Eight out of 101 (8%) patients with hereditary OC and five out of 127 (4%) patients with hereditary BC carried pathogenic mutation in one of MMR genes. Average age of manifestation of BC and OC in the patients with Lynch syndrome was 54 y.o. in case of OC and 56 y.o. in case of BC group: 50 y.o. Nine women had first and second-degree relatives with either BC, OC, colon or esophagus cancer. The distribution of affected genes in HBOC cohort was as follows: 3 patients with mutation in MSH6 gene, 4 patients with mutation in PMS2 gene, 2 patients with mutation in MSH2 gene, 3 patients with mutation in mlH1 gene. One patient carried mutation in EPCAM gene.

Conclusions

To date, the clinical standard for screening for Lynch syndrome is the Amsterdam criteria II, which are not oriented to the occurrence of OC and BC in patients, as well as to the presence of these cancers in a hereditary history in patients with colorectal cancer. However, our experience shows that patients with signs of hereditary OC and BC also can be carriers of mutations in the genes of the MMR system, which determine the Lynch syndrome. Thus, impact of Lynch syndrome-associated germline mutation on other types of cancer should be reconsidered and studied in detail.

Legal entity responsible for the study

Tatarstan Cancer Center.

Funding

The work is supported by the Russian Foundation for Basic Research № 18-415-160009 r_a and according to the Russian Government Program of Competitive Growth of Kazan Federal University.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

242P - Impact of deleterious germline BRCA mutations, addition of taxanes and use of adjuvant endocrine therapy (ET) on anti-müllerian hormone (AMH) levels in early breast cancer (EBC) patients treated by adjuvant chemotherapy (CT)

Presentation Number
242P
Lecture Time
12:45 - 12:45
Speakers
  • Nathalie OLYMPIOS (Rouen, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

AMH is a promising biomarker of treatment-induced gonadal damage. The impact of carrying a deleterious germline BRCA mutation, adding a taxane to anthracycline-based CT and using adjuvant ET on gonadal function following CT remains unclear. We assessed the influence of these 3 factors on AMH levels before and after adjuvant CT in EBC patients.

Methods

This monocentric retrospective study included consecutive EBC patients aged ≤40 years treated with adjuvant FEC CT between 2008 and 2016, known germline BRCA status and available frozen plasma samples before and after CT. AMH levels (ng/mL) were assessed before starting CT, 1 year and over 3 year after diagnosis.

Results

148 patients were included. 35 (24%) patients harbored a deleterious germline BRCA mutation, 127 (86%) received a taxane following FEC CT and 90 (61%) had adjuvant ET after CT. Overall median age was 35 (range 22-40). In the whole cohort, median AMH levels dropped after adjuvant CT (from 1.69 to 0.06, p < 0.0001) and slightly recovered after 3 years (0.17, p < 0.0001). No difference in baseline (1.94 vs 1.66, p = 0.53), 1-year (0.09 vs 0.06, p = 0.39) or 3-year (0.25 vs 0.16, p = 0.43) AMH levels was observed between patients with or without a BRCA mutation. Significant lower AMH levels were observed for patients who received a FEC-taxane regimen as compared to those treated with FEC only CT 1 year after diagnosis (0.04 vs 0.22, p = 0.0006), with no difference at 3 years (0.18 vs 0.06, p = 0.47). Patients treated with adjuvant ET had slightly higher AMH levels than those who did not receive ET 1 year after diagnosis (0.12 vs 0.02, p = 0.008) with no difference at 3 years (0.11 vs 0.20, p = 0.22).

Conclusions

Use of adjuvant CT is associated with a significant and durable alteration in ovarian reserve measured by AMH levels. Addition of taxanes to FEC increased CT-induced gonadotoxicity immediately after CT exposure but not at longer follow-up. Carrying a germline BRCA mutation and using adjuvant ET following CT were not associated with additional negative impact on patients’ ovarian reserve after treatment.

Legal entity responsible for the study

Centre Henri Becquerel, Rouen, France.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

243P - Germline mutation status and therapy response in patients with triple-negative breast cancer (TNBC): Results of the GeparOcto study

Presentation Number
243P
Lecture Time
12:45 - 12:45
Speakers
  • Esther Pohl (Cologne, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The phase III neoadjuvant GeparOcto trial (NCT02125344) randomized patients with triple negative breast cancer (TNBC) to receive treatment with intensified dose-dense epirubicin (E), paclitaxel (P), and cyclophosphamide (C; iddEPC) or weekly paclitaxel/liposomal doxorubicin (PM), plus carboplatin (Cb). Data on germline mutational analysis of patients with TNBC and the correlation with pathological complete response (pCR ypT0/is ypN0) were analysed.

Methods

NGS-based germline mutational analysis of BRCA1/2 and further 16 BC predisposition or candidate predisposition genes was carried out in 393 patients (iddEPC n = 194, PMCb n = 199). Deleterious (IARC class 4/5) variants were validated by Sanger sequencing. Detection of copy number variations (CNV) was carried out using an in-house CNV detection tool and established open access tools. Validation of CNVs was performed by either multiplex ligation-dependent probe amplification or real-time PCR.

Results

Overall, 69 of 393 (17.6%) patients carry pathogenic mutations in the BRCA1/2 genes. In 324 BRCA1/2-negative patients, 30 patients carry mutations in at least one of the 16 further analysed genes (9.3%). Of those, two patients carry mutations in two genes (ATM/CHEK2, PALB2/XRCC2) and 28 carry mutations in one gene (n = 2 BARD1, n = 5 BRIP1, n = 1 CHEK2, n = 9 FANCM, n = 1 NBN, n = 8 PALB2, n = 1 RAD50, n = 1 RAD51C); no mutations were found in CDH1, MRE11A, PTEN, RAD51D, STK11, and TP53). Overall patients with a BRCA1/2 mutation had a pCR of 69.6% vs 46.0% without a mutation (p < 0.001). In the iddETC group, patients with a BRCA1/2 mutation had a pCR of 64.7% vs 45.0% without a mutation (p = 0.040); in the PMCb arm, patients with a BRCA1/2 mutation had a pCR of 74.3% vs 47.0% without a mutation (p = 0.005).

Conclusions

Our data confirm that BRCA1/2 germline mutations represent a predictive biomarker for the achievement of pCR following neoadjuvant anthracycline-taxane-containing chemotherapy for TNBC.

Clinical trial identification

NCT02125344.

Legal entity responsible for the study

German Breast Group (GBG).

Funding

German Breast Group (GBG).

Disclosure

A. Schneeweiss: Honoraria: Roche, Celgene, AstraZeneca, Novartis, and Pfizer during the past 2 years. C. Hanusch: Consulting or advisory role: Novartis, Roche, Amgen, and Celgene during the past 2 years; Speakers’ bureau: Novartis, Roche, Amgen, Pfizer, and Celgene during the past 2 years. V. Müller: Honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, Novartis, Roche, and Teva during the past two years; Consulting or advisory role: Hexal, Roche, Pfizer, Amgen, Daiichi Sankyo, Nektar, and Eisai during the past 2 years; Travel, accommodation, or other expenses paid or reimbursed: Roche and Pfizer during the past 2 years. K. Luebbe: Consulting or advisory role: Roche and Novartis during the past 2 years. S. Loibl: Honoraria: Pfizer and Roche during the past 2 years (institution); Consulting or advisory role: Novartis, Pfizer, Roche, and SeaGen during the past 2 years (institution); Research project funding: Abbvie, Amgen, AstraZeneca, Celgene Novartis, Pfizer, Roche, SeaGen, Teva, and Vifor during the past 2 years (institution). All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

244P - BRCA1/BRCA2 Predictive Genetic Testing in an Irish Population: A Missed Opportunity

Presentation Number
244P
Lecture Time
12:45 - 12:45
Speakers
  • David E. O Reilly (Dublin, IE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The diagnosis of a BRCA1/2 mutation has significant implications for both probands and their families, with both screening and prophylactic surgical interventions available. Underutilisation of genetic testing services has been reported in other jurisdictions. BRCA1/2 testing is requested in only 29-53% of eligible women and 11-12% of eligible men, represented a missed cancer prevention opportunity. Possible explanations include lack of family disclosure, poor access or lack of awareness of genetic counselling services, or patient preference. We investigated the rates of BRCA1/2 predictive testing in an Irish population.

Methods

We performed a multicentre, retrospective analysis of 63 pedigrees from two Irish tertiary hospitals over a five-year period (2012-2017). By manually examining pedigrees, we identified eligible family members who should receive BRCA1/2 mutation testing as per national guidelines.

Results

A total of 1048 candidates for predictive BRCA1/2 mutation testing were identified. 318 (30.4%) proceeded to BRCA1/2 mutation testing including 215 (37.5%) females and 99 males (21.5%). Uptake of testing favouring women was statistically significant (T = 3.7, p<.0002).

Conclusions

We demonstrate suboptimal uptake of BRCA1/2 mutation testing in the Irish population, particularly among Irish males. Predictive BRCA1/2 testing and subsequent screening/surveillance/prophylactic intervention in mutation carriers can meaningfully impact breast cancer survival. This represents a missed cancer prevention opportunity for Irish society.

Legal entity responsible for the study

Department of Cancer Genetics, St. James' Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

245P - Incidence and Survival among Young Women with Stage I-III Breast Cancer

Presentation Number
245P
Lecture Time
12:45 - 12:45
Speakers
  • Alexandra Thomas (Winston Salem, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

De novo Stage IV breast cancer (BC) is increasing in premenopausal women. Less is known about current incidence and survival among these women with Stage I-III BC.

Methods

Women ages 20-29 (N = 3,826), 30-39 (N = 34,585), 40-49 (N = 126,552) and 50-59 (N = 172,448) diagnosed with Stage I-III BC from 2000-15 were identified from the US Surveillance, Epidemiology and End Results database. Age-adjusted, annual percentage changes (APC) in incidence and 10-year Kaplan-Meier survival curves were estimated by stage, hormone receptor (HR) status, and grade (low: well/moderately differentiated; high: poorly/undifferentiated) for each age decade.

Results

Stage III BC at presentation decreased with age (20-29 [23.9%], 30-39 [21.9%], 40-49 [16.1%], 50-59 [14.1%]); the opposite pattern was observed for Stage I (23.6%, 28.8%, 42.0%, 48.3%, respectively). HR+ high grade and HR- BCs also decreased with age (20-29 [34.5%, 36.5%], 30-39 [31.1%, 31.6%], 40-49 [23.9%, 21.4%], 50-59 [20.9%, 21.1%]). Among all BC presentations, age-adjusted APC in incidence was higher for women 20-29 (1.6) than those 30-39 (0.3), 40-49 (0.3) or 50-59 (-1.1). Incidence of HR+ low and high-grade BC increased for women <50 with the highest APC (5.7 and 3.8, respectively) for women 20-29; HR- BC incidence decreased for all ages. Among women 20-29, 10-year survival was lowest for those with HR+ high grade BC (Table); for this group, the greatest survival difference between HR+ high grade and HR- BC was for Stage I BC (79.8% vs 89.3%) compared to Stage II (77.2% vs 80.7%) or Stage III (44.9% vs 45.0%). Comparing Stage III BC across age decades, 10-year survival was lowest for women 20-29, notably for HR+ BC.

StageHR StatusGrade10-Year Survival % (Standard Error)
Age (years)
20-2930-3940-4950-59
Any+Low81.2 (1.9)85.4 (0.5)91.1 (0.2)89.2 (0.1)
+High67.7 (2.0)75.3 (0.6)80.2 (0.3)77.1 (0.3)
-73.8 (1.5)74.3 (0.5)75.1 (0.3)74.3 (0.3)
Stage III+Low54.2 (5.7)62.8 (1.6)73.7 (0.7)68.3 (0.7)
+High44.9 (3.9)55.7 (1.3)60.1 (0.8)54.2 (0.8)
-45.0 (3.5)49.2 (1.2)49.8 (0.8)47.5 (0.7)

Conclusions

Among young women, HR+ BC is increasing in incidence and associated with reduced survival for those 20-29. Understanding the etiologies underlying these trends may inform strategies directed toward improving outcomes for these women.

Legal entity responsible for the study

University of Iowa.

Funding

United States Centers for Disease Control and Prevention (U01DD001035) and the Nealie Belk Stevens Fund for Breast Cancer Research.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

246P - Toxicity and Clinical Outcomes of Partial Breast Irradiation (PBI) Compared to Whole Breast Irradiation (WBI) for Early Stage Breast Cancer: A Systematic Review and Meta-analysis

Presentation Number
246P
Lecture Time
12:45 - 12:45
Speakers
  • Hadar Goldvaser (Toronto, CA)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

There is uncertainty about efficacy and toxicity differences between adjuvant PBI and WBI in women with early-stage breast cancer treated with breast conservation.

Methods

We identified randomized trials that compared PBI to WBI in early-stage invasive breast cancer using PubMed. Odds ratios (ORs), 95% confidence intervals (CI) and absolute risks were computed for pre-specified efficacy and toxicity outcomes including cosmetics. Subgroup analysis evaluated the effect of PBI modality (external beam radiation treatment [EBRT], intraoperative radiation treatment [IORT] or brachytherapy) on efficacy. Meta-regression analysis explored the influence of median follow-up as well as patients and tumor characteristics on results.

Results

Eight trials comprising 10298 patients were included. Efficacy results, weighted absolute differences and subgroup analysis are shown in the table. PBI was associated with increased odds of local recurrence compared to WBI. However, PBI was associated with reduced odds of death without breast cancer recurrence and improved overall survival (OS). Subgroup analysis showed the effect on local recurrence was influenced by modality of radiation; odds of local recurrence were increased with IORT and brachytherapy, but not with EBRT. Nodal involvement was associated with higher local recurrence risk while larger tumors were associated with lesser improvement in death without breast cancer recurrence and OS. PBI was associated with higher odds of fat necrosis (p = 0.002). Worse cosmetic outcome with PBI approached significance (p = 0.06).

OR, 95% CIP value all/ subgroup differenceWeighted absolute difference
5-year local recurrence
All2.28 (1.66-3.15)<0.0011.47%
EBRT IORT Brachytherapy0.64 (0.25-1.62) 3.1 (2.12-4.51) 1.44 (0.63-3.29)0.004
5-year regional recurrence
All1.49 (0.88-2.53)0.140.3%
EBRT IORT Brachytherapy1.96 (0.20-18.92) 1.45 (0.80-2.63) 1.56 (0.39-6.27)0.97
5-year contralateral breast cancer
All0.94 (0.59-1.47)0.77-0.1%
EBRT IORT Brachytherapy0.85 (0.44-1.63) 1.54 (0.65-3.66) 0.64 (0.25-1.62)0.37
5-year death without breast cancer recurrence
All0.55 (0.41-0.73)<0.001-1.6%
EBRT IORT Brachytherapy0.71 (0.42-1.20) 0.45 (0.29-0.69) 0.57 (0.29-1.13)0.41
5-year overall survival
All0.76 (0.61-0.95)0.02-1.1%
EBRT IORT Brachytherapy0.79 (0.51-1.22) 0.78 (0.59-1.04) 0.61 (0.32-1.14)0.75

Conclusions

Compared to WBI, PBI is associated with higher odds for local recurrence and toxicity, but less death without breast cancer recurrence and improved OS. The balance between benefit and risk of PBI appears optimal for women with smaller ER positive tumors and without nodal involvement.

Legal entity responsible for the study

Hadar Goldvaser.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

247P - Should anthracyclines always be present in the adjuvant treatment of breast cancer (BC)? A systematic review and meta-analysis of randomized controlled trials (RCTs)

Presentation Number
247P
Lecture Time
12:45 - 12:45
Speakers
  • Rafael Caparica (Brussels, BE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Anthracycline and taxane-based (A+T) chemotherapy (CT) is the current standard adjuvant CT for HER2-negative BC patients. However, anthracyclines can be associated with important short and long-term toxicities (e.g. cardiotoxicity and leukemias). After a phase 3 trial demonstrated that docetaxel+cyclophosphamide (TC) was more effective than doxorubicin + cyclophosphamide (AC), the use of TC has increased. Nevertheless, RCTs could not demonstrate that TC is non-inferior to the standard A+T. This is a systematic review and meta-analysis of RCTs comparing A+T versus TC as adjuvant CT in HER2-negative BC patients.

Methods

A literature search using PubMed, EMBASE, Cochrane, ASCO, ESMO and SABCS websites was performed up to March 30, 2018, to identify RCTs comparing TC vs A+T as adjuvant CT in HER2-negative BC patients. Disease-free survival (DFS) and overall survival (OS) were assessed. A subgroup analysis of DFS in hormone receptor positive (HR+) and negative (HR-) disease was also performed. Hazard ratios (HR) and 95% confidence intervals (CI) for DFS were extracted from each trial, and a pooled analysis was conducted using the random-effect model. The Higgins' I-Squared Test was used to quantify heterogeneity.

Results

A total of 8 RCTs that randomized 12,741 early BC patients were included. Five RCTs were published as pooled results: ABC trials comprised 3 RCTs, and PlanB + Success-C comprised 2 RCTs. The comparison of TC versus A+T demonstrated a non-significant benefit in favour of A+T for both DFS (HR 1.08, 95% CI 0.96 - 1.20) and OS (HR 1.05; 95%CI 0.90 – 1.22). The magnitude of the benefit of A+T was more pronounced in patients with HR- disease, (N = 1,947, HR 1.12, 95% CI 0.93 – 1.34) compared to those with HR+ disease (N = 4,867, HR 1.05, 95%CI 0.86 – 1.27).

Conclusions

Globally, our results showed that A+T was associated with a slight non-significant improvement in DFS and OS as compared to TC. Nevertheless, in selected patients such as those with HR+ disease, TC may be considered an alternative option to avoid the toxicities of anthracycline-based CT.

Clinical trial identification

CRD42018090962 - PROSPERO register.

Legal entity responsible for the study

Institut Jules Bordet.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

248P - Taxane & Cyclophosphamide vs Anthracycline & Taxane combination therapy as adjuvant treatment of breast cancer; a meta-analysis of randomized-controlled trials by the Hellenic Academy of Oncology (E.AK.O.)

Presentation Number
248P
Lecture Time
12:45 - 12:45
Speakers
  • Panagiotis Ntellas (Larissa, GR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Adjuvant chemotherapy has an indisputable value for early breast cancer. Τaxane + cyclophosphamide combination (TC) has demonstrated superiority against cyclophosphamide + anthracycline (AC) in disease-free (DFS) and overall survival (OS). However, 5 randomized clinical trials (RCTs) failed to show non-inferiority of TC compared to an anthracycline-taxane combination (TaxAC). We conducted a meta-analysis of these RCTs to better estimate the cumulative evidence for non-inferiority of TC against TaxAC, in the adjuvant setting of HER2-negative, breast cancer.

Methods

The ABC trials, the Plan B trial and a trial by the Hellenic Oncology Research Group (HORG) were meta-analyzed. The DFS was the primary endpoint. A DFS-HR of 1.18 for TC versus TaxAC, was chosen to demonstrate inferiority, as it was the most conservative measure among the included studies. Secondary endpoints were OS and toxicity profile.

Results

Overall, 7,341 patients composed the meta-analysis population. We didn’t encounter heterogeneity between the trials (Q-test p = 0.55, I2:0%) and no publication bias was detected. Non-inferiority of TC was not established (DFS-HR=1.11, 95%CI: 0.95-1.30, p = 0.18). The combined DFS rates, according to the time points set by each study, were 89.04% versus 90.35% for TC and TaxAC respectively. Non-inferiority of TC was also not proven for the node-negative population either (HR = 1.05, 95%CI: 0.82-1.34, p = 0.71). Grade 3-4 leucopenia (OR: 1.2, 95%CI:1.068-1.348, p = 0.002) and thrombocytopenia (OR = 6.455; 95%CI:2.902-14.359, p < 0.001) prevailed in the TaxAC group, while cardiotoxicity was also increased (OR = 2.283; 95%CI:1.155-4.514, p = 0.015).

Conclusions

Although the TC combination was not proven to be non-inferior to TaxAC, the present analysis narrows the HR of recurrence risk of recurrence with a difference in the DFS rate of only 1,31%. Taking into account the more favorable safety profile of the TC combination, the question as to which treatment regimen should be preferred under what circumstances needs to be individualized according to patients’ characteristics and desires.

Legal entity responsible for the study

Hellenic Academy of Oncology.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

249P - Risk of cardiovascular late effects in breast cancer survivors: a population-based study

Presentation Number
249P
Lecture Time
12:45 - 12:45
Speakers
  • Jihyoun Lee (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Cardiovascular diseases are one of the late effects of breast cancer treatment that can impair survival. We reviewed the development of cardiac disease in breast cancer survivor using nationwide database.

Methods

A nation-wide retrospective cohort study was conducted using National Health Information Database which provides a whole set of claimed medical information, such as ICD-10 diagnosis and prescription data. We performed 1:5 age-sex matching with the non-cancer controls. Incidence of MI and CHF was evaluated for adjuvant treatment modalities, with adjustment of age and previous comorbidities (diabetes, hypertension, and hyperlipidemia).

Results

A total of 112,058 cases (554,801 person-years) and 560,290 controls (2,916,459 person-years) were evaluated. Risk of MI (hazard ratio (HR) 1.258, 95% confidence interval (CI) 1.168 - 1.355) and CHF (HR 1.86, 95% CI 1.753 – 1.973) was higher in breast cancer survivors than in non-cancer controls. Younger survivors (age 50 or less) showed the highest risk of MI (HR 1.73, 95% CI 1.512 – 1.979) and CHF (HR 3.557, 95% CI 3.174 – 3.986). Within one year of breast cancer diagnosis, the cumulative incidences of MI and CHF were significantly high in survivors. The cumulative incidence of CHF in breast cancer survivors was continuously higher than the control group, in contrast to that of MI showed similar pattern to controls. Taxane use was associated with development of MI (HR 1.284, 95% CI 1.074 – 1.534) and CHF (HR 1.65, 95% CI 1.444 – 1.887).

Conclusions

Incidence of MI and CHF were higher in breast cancer survivor than the non-cancer controls. The elevated risk of MI and CHF in early phase of survivorship should be noted, especially in young age group.

Legal entity responsible for the study

The Study of Multi-disciplinary Teamwork for breast cancer survivorship (SMARTSHIP).

Funding

Korean Breast Cancer Society.

Editorial Acknowledgement

The authors appreciate to the Korean Breast Cancer Society and the Study of Multi-dicsiplinary Teamwork for breast cancer survivorship (SMARTSHIP)

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

250P - Diagnostic Value of Contrast Enhanced Digital Mammography versus Contrast Enhanced MRI for Preoperative Evaluation of Breast Cancer

Presentation Number
250P
Lecture Time
12:45 - 12:45
Speakers
  • Eun Young Kim (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

This study aimed to compare the diagnostic performance of pre-operative evaluation of contrast-enhanced digital mammography (CEDM) and contrast-enhanced magnetic resonance imaging (CEMRI) and to evaluate the effect of each modality to the surgical management in women with breast cancer.

Methods

This single-institution prospective study was approved by the Institutional Review Board and informed consent was obtained from all patients. From November 2016 to October 2017, 84 patients, who were diagnosed as invasive carcinoma (69/84) and ductal carcinoma in situ (DCIS) (15/84) underwent both CEDM and CEMRI, were enrolled. We correlated the imaging findings and surgical management with pathologic results, and compared the diagnostic performance of both modalities in the detection of index and secondary cancers (multifocality and multicentricity), and occult cancer in contralateral breast. We also evaluated whether CEDM or CEMRI made changes in surgical management of the affected breast attributed to imaging-detected findings.

Results

Eighty-four women were included for analysis. CEDM, in comparison to CEMRI, had a significantly higher specificity (66.7% vs 22.2%, P = 0.021), similar sensitivity (94.6% [78/84] vs 93.5% [81/84]), PPV (93.5% vs 86.0%) and a fewer false positive findings (66.7% [10/15] vs 93.3% [14/15]) in detecting index cancer. For detection of secondary cancers on ipsilateral breast and occult cancer in contralateral breast, no significant differences were found between CEDM and CEMRI (all P > 0.05). Regarding changes in surgical management, CEDM made less change (36.9% [31/84] vs 41.7% [35/84]) than CEMRI, owing to less false positive findings (48.4% [15/31] vs 54.3% [19/35]).

Conclusions

CEDM showed comparable diagnostic performance with CEMRI in depicting index, secondary cancers, and occult cancer in contralateral breast. The CEDM, owing to fewer false positive results, made less change in surgical management compared to CEMRI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

251P_PR - Pregnancies after breast cancer, is there a real need for fertility preservation ? Results from the ARTEMIS cohort of 60 young patients

Presentation Number
251P_PR
Lecture Time
12:45 - 12:45
Speakers
  • Jerome Martin-Babau (Plérin, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

One of the main problems affecting young women after adjuvant chemotherapy for early breast cancer is the desire for children and the impact of the treatment on this desire and on pregnancy. Many works are ongoing on fertility preservation but what is the real need ? Hence a survey to evaluate these issues in young breast cancer survivors was put in place.

Methods

Patients aged between 18 and 40 years old treated by chemotherapy for non-metastatic breast cancer between 2005 and 2017 were retrospectively asked to respond to this survey, after having signed a consent form.

Results

96 patients were identified, from which 60 agreed and responded to the survey. This high response rate demonstrates the importance of these themes for patients.

Median age at diagnosis was 36 years old (34-40).

Median time between the end of chemo-/radiotherapy and inclusion was of 57 months.

34 patients had node involvement at diagnosis, 10 patients had triple negative tumors.

Adjuvant endocrine therapy was prescribed in 70% of patients from whom 54% were still under treatment at inclusion. Tamoxifen was prescribed in 90% of the cases and complete ovarian suppression for 9.5% of the patients. The mean treatment time was 5 years.

The survey showed that anticancer treatments had a major impact on patients:

Chemotherapy-induced amenorrhea was experienced by 83% of the patients but 86% recovered normal cycles in the following months.

Diagnosis and treatment affected the patients desire for pregnancy: indeed before diagnosis, 31% were hoping to become pregnant; this desire fell to 10% after treatment. However, of these 6 patients: 2 patients became pregnant and 2 miscarried.

Patient’s relationships were affected as 20% declared a change of partner directly or indirectly related to the treatment.

Sexual quality-of-life was impacted in 61% of patients with long-term side effects.

Conclusions

Treatment of breast cancer impacts strongly the quality of life of young breast cancer survivors.

However, definitive amenorrhea related to chemotherapy in these patients occurred in a minority of them and the number of pregnancies reported after treatment is higher than expected if we take into account the desire of pregnancy after treatment.

Clinical trial identification

NCT03470935

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

252P - Relationship between androgen receptor and tumor infiltrating lymphocytes in triple negative breast cancer

Presentation Number
252P
Lecture Time
12:45 - 12:45
Speakers
  • Luis Felipe Sánchez-Cousido (Leon, ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Triple-negative breast cancer (TNBC) is considered a poor prognostic subtype and a heterogeneous entity. Its only treatment is chemotherapy. Immunotherapy and antiandrogen therapies are being tested. Androgen receptor (AR) is expressed in up to 53% of TNBC. It is associated with a better disease-free survival and overall survival. The relation between tumor infiltrating lymphocytes (TIL) and AR in urothelial cancers has been assessed, unlike in TNBC.

Methods

50 stage I-III TNBC patients diagnosed between 2008 and 2013 were analyzed. Minimum follow-up was 57 months or until death. On these samples fixed in 10% formalin and included in paraffin, the evaluation of the expression of AR, CD20, CD4 and CD8 was performed by immunohistochemistry. AR+ was defined by more than 1% expression. Lymphocytes were evaluated as per the recommendations of the International Expert Consensus. We also analyzed total lymphocytes as high/low if they were over/under 80%. Data was analyzed by SPSS version 23.

Results

Clinical characteristics are as follows: mean age of 61 years old, and postmenopausal 68%. 74% of the patients did not relapse and progression-free survival (PFS) was 95,6 months. Main tumor characteristics were Ki67>20%, 67,3%; T1-T2 88%; high grade 67,4%; lymph node (N) positive 51%. Early stage (stage I-II) was the 80%. High level of lymphocytes (HiL) was present in 70% of them. AR + (26%) was associated with younger patients (p = 0.009), low Ki67 (p = 0.014) and N + (p=0.025). No relation was obtained between AR and TIL, tumor size, grade, stage or survival. CD8+ were more present in AR + (p=0.002) and so the proportion CD4/CD8 (CD8>CD4 in AR+; CD4>CD8 in AR-. p = 0.026) HiL was related with higher Ki67 (p = 0.021) and grade 3 (p = 0.029). However, lower relapse and also lower deaths were observed in those with HiL (15.4% vs 84.6%; 21.4% vs 78.6%). In HiL, percentage of CD8+ was inversely proportional (p = 0.021 mean 27,7%).

Conclusions

High grade tumors and higher Ki67 unleash a higher immune response, protecting from a worse prognosis. CD8+ lymphocytes are associated with AR expression. More studies are needed to understand the relationship between AR and TIL and also the role of AR blockade in TNBC and its role in immune-mediated lysis.

Legal entity responsible for the study

Complejo Asistencial Universitario de León.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

253P - Use of red clover in premenopausal breast cancer patients receiving hormonal adjuvant treatment: biological and clinical implications from a randomized clinical trial

Presentation Number
253P
Lecture Time
12:45 - 12:45
Speakers
  • Cristina Ferraris (Milan, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Premenopausal women with breast cancer (BC) experience early onset of treatment-induced menopausal syndrome with adjuvant hormone therapy (HT). Isoflavones in the red clover (RC) are biologically active agents providing a source of rapidly available phytoestrogens acting as natural selective estrogen receptor modulators. Aims of the study are: to improve quality of life reducing menopausal symptoms from HT in BC premenopausal women and preventing weight gain and metabolic syndrome with personal lifestyle intervention; to evaluate in vitro safety profile of RC used in combination with adjuvant anti-estrogenic HT.

Methods

Eighty-eight premenopausal BC women (DCIS, T1/T2N0-N1M0) receiving adjuvant HT were randomly assigned to have 80 mg/die of RC dry extract (MCE-11) (verum group) or a tablet without active principle (placebo group) for 2 years. Menopausal Rating Score (MRS) questionnaire was given every three months during the first year then biannually. Diet program was personalized with the WCRF/AICR recommendations and Mediterranean diet. Body Max Index (BMI), hip and waist circumference, homeostatic model assessment index (HOMA) and lipid profile (total LDL, HDL cholesterol, triglycerides) were recorded. Pool serum of women from the two groups was run for in vitro evaluation of the safety profile using specific cell lines selected to be representative of hormone-sensitive BC with high expression of estrogen receptor a (MCF7, T47D) and β (BT20).

Results

Menopausal symptoms significantly decreased in both groups over time (p < 0.0001). In the verum group BMI, hip and waist circumference were more reduced than in placebo group (P < 0.0001). HDL cholesterol significantly improved over time (p < 0.01). There was no significant difference in endometrial rhyme, while mammary density significantly decreased in both arms (p < 0.0001). In vitro, no significantly differences were observed in cell growth and induction of estrogen regulated/related genes in the cell lines treated with serum from women of the two arms.

Conclusions

Isoflavones can be safely used in premenopausal BC women under HT to contrast symptoms related to treatment.

Clinical trial identification

Protocol number INT 101/11 release date 25/06/2012 - EudraCT: 2011-005518-12 2-2-24-01-2012.

Legal entity responsible for the study

Cristina Ferraris.

Funding

Named S.p.A.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

254P - PROMs following breast-conserving therapy for breast cancer: results from a prospective longitudinal monocentric study

Presentation Number
254P
Lecture Time
12:45 - 12:45
Speakers
  • Isabelle Kindts (Leuven, BE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

To evaluate patient-reported outcomes (PROs) and long-term aesthetic outcome (AO) related to radiotherapy (RT) in the breast-conserving therapy setting for breast cancer over time. To explore the agreement between PROs and AO.

Methods

Patients treated with breast-conserving therapy at one institute between April 2015 and April 2016 were prospectively included in the cohort. The AO was scored by the patient and by the BCCT.core software. Further PROs were measured with the EORTC QLQ-C30, QLQ-BR23 and the BIBCQ. Patients were evaluated at preset time points over two years. First, we assessed the evolution in time of the PROs and AO. Second, we tested the differences in mean scale scores of the PROs between patients with a favourable and an unfavourable AO.

Results

175 patients were included in the analysis. At baseline unsatisfactory levels were already present for several global, functional, symptom and body image scales. Most unsatisfactory PROs improved significantly up to one year after RT. Fatigue showed a small deterioration at the start of RT, but improved medium thereafter up to one year after RT (mean difference (MD) 7.6, -12.3, respectively and p < 0.001). Cognitive functioning showed a small decrease from at the start of RT with no further significant decrease (MD -4.73, -0.21 and p 0.003, 0.894, respectively). Breast symptoms significantly increased during RT but decreased afterwards up to two years after RT to lower values than at baseline and were then considered satisfactory (MD 15.6, -19.7, -4.1 and p < 0.001, <0.001, 0.005, respectively). AO scored by the patient and with the BCCT.core associated well with each other and with the body image measures. There was no association between AO and global cancer-related QOL in the present cohort.

Conclusions

Small quality of life impairments present during RT with good recovery up to one year after RT. Body image is disturbed during RT and improves up to two years after RT. Around one third of patients score their long-term AO as unfavourable and these PROs correlate well with body image.

Legal entity responsible for the study

Caroline Weltens.

Funding

Kom Op Tegen Kanker.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

255P - Impact on disease-free survival (DFS) of the surgical waiting time (SWT) for patients (Pts) with early breast cancer (BC)

Presentation Number
255P
Lecture Time
12:45 - 12:45
Speakers
  • RIKIYA Nakamura (Chiba, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

SWT is distressing for patients and impairs their quality of life. There are few studies and no consensus in the literature concerning the impact of BC biology on SWT, particularly in each subtype. However, a randomized trial is not possible to study the SWT. We aimed to assess the impact of the SWT and the histological grade (HG) of tumor on DFS.

Methods

We retrospectively reviewed the data of Pts with invasive BC who received core needle biopsy (CNB) as diagnosis between January 2007 and June 2017. Pts who required neo-adjuvant chemotherapy were excluded. The primary analysis was a comparison of the DFS between patients who have SWT for 1 month or less (early group) and those who have them for longer than 1 month (late group). Propensity score matching in these groups was calculated based on the menopausal status, cT, cN, ER, PgR and HER2 status. Furthermore, we divided the Pts into 4 groups for the survival analysis as follows: the HH [high grade CNB/high grade surgical specimen (SS)], the LL (Low grade CNB/Low grade SS), LH (Low grade CNB/high grade SS) and the HL group (high grade CNB/low grade SS).

Results

We analyzed the data of 1513 patients. Based on the propensity score, the early group and late group had 530 matched patients each. The median age was 62 years, cT1:58%, cT2:36%, cN0:75%, cN1;25%, ER(+) 82%, PgR(+) 68%, HER2(+):12% in both groups. The median diagnosis to curative SWT was 24.2 days in the early group and 46.7 days in the late group. A propensity score-matched model showed the significant difference in the DFS between the early group and the late group (5-year DFS rate, 92.9 vs. 86.6%; p = 0.0014 HR:1.98 1.30 to 3.08). Multivariate analysis revealed that the prognostic factors were significantly associated with cT (HR:2.02 95% CI 1.34 to 3.07), cN (HR:2.68 95% CI 1.78 to 4.04) and SWT (HR: 1.98, 95% CI, 1.30 to 3.08). ER, PgR and HER2 were not independent prognostic factors. The LH group for early group had a shorter DFS than the HL, HH and LL group (p = 0.0013). The HG for late group was not associated with survival.

Conclusions

The late group was significant worse in DFS compared with the early group. The histological up-grading of tumor for the early group was associated with worse survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

256P - Oncological outcome of fat grafting for breast reconstruction after cancer

Presentation Number
256P
Lecture Time
12:45 - 12:45
Speakers
  • Gaia Griguolo (Bellinzona, CH)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Fat grafting (FG) has become widely used in breast reconstruction after breast cancer (BC). FG might express protumorigenic factors or alter radiological aspect of the breast, raising some concerns on its oncological safety. The aim of the study was to describe clinical outcome of patients (pts) undergoing FG.

Methods

Records of 424 pts who underwent FG between 2010 and 2017 at the Plastic Surgery Dept. of Padova University were reviewed. Pts without invasive BC or not followed at Istituto Oncologico Veneto were excluded, leaving 206 pts for analysis. Cumulative Incidence of relapse was calculated from first FG. Association between clinico-pathological factors and relapse was explored.

Results

Patients were mostly post-menopausal (n = 115, 56%) and the majority had HR+/HER2- BC (n = 134, 65%). Eight pts (4%) were BRCA-mut carriers. Disease stage at diagnosis was: I (42%), II (34%), III (24%). Median interval from surgery to first FG was 23 months (range 0-257). 336 FG interventions were performed (median per patient: 1, range 1-9). At median follow-up of 38.9 months, 35 pts relapsed (10 locoregional, 25 distant relapses). Cumulative Incidence of relapse according to clinico-pathological subgroups is reported in the table. Semestral hazard rates of relapse in the three years after FG were: 0.010, 0.053, 0.034, 0.007, 0.039, and 0.038, respectively. 59 pts (29%) underwent additional breast imaging over standard recommendation (range 1-6 per patient), and 40 (20%) pts underwent breast biopsies (range 1-4, 10 confirmed a local recurrence).

Clinicopathological factorsNumber of patients (%)3-years cumulative incidence of relapseHazard Ratio (95% CI)
HR statusHR negative26 (13%)13%ref
HR positive170 (87%)16%1.57 (0.47-5.18)
HER2 statusHER2 positive46 (24%)10%ref
HER2 negative143 (76%)16%1.93 (0.74-2.05)
Stage at diagnosisStage I81 (42%)11%ref
Stage II67 (34%)17%2.84 (1.06-7.62)
Stage III47 (24%)23%4.42 (1.68-11.63)
Interval from surgery to first FG>2 years99 (48%)16%ref
<2 years107 (52%)17%1.07 (0.55-2.08)
Type of breast surgeryMastectomy180 (87%)15%ref
Conservative26 (13%)25%1.53 (0.63-3.69)
Overall Population206 (100%)17%-

Conclusions

This study describes a not negligible rate of recurrence in BC pts receiving FG, especially in stage III and conservative surgery pts. High risk of relapse in the first years after FG might suggest a potential relation between the procedure and events. Moreover, a significant proportion of pts underwent additional breast imaging and biopsies, which can adversely affect quality of life. A careful discussion in multidisciplinary setting is crucial for proper pts selection.

Legal entity responsible for the study

Valentina Guarneri.

Funding

Has not received any funding.

Editorial Acknowledgement

No editorial assistance was provided by a third party for the abstract.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

257P - Changes in body weight over 18-months follow-up among Chinese patients after breast cancer diagnosis

Presentation Number
257P
Lecture Time
12:45 - 12:45
Speakers
  • Winnie Yeo (Shatin, HK)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Weight gain has commonly been reported among patients after breast cancer diagnosis in western countries. Based on limited data in the literature, weight gain in Asian counterparts appears to be less. In this prospective study, we investigate the weight changes among Chinese breast cancer patients during 18-month follow-up from diagnosis.

Methods

This is part of the ongoing Hong Kong NTEC-KWC Breast Cancer Survival Study (HKNKBCSS). Chinese patients with newly diagnosed early-stage breast cancer were consented. Studied patients had their weights recorded at breast cancer diagnosis (T0), at study entry (T1; within 12 months from T0) and at 18-month follow-up (T2). Potential associating factors including socio-demographic, lifestyle and clinical factors were assessed.

Results

A total of 1265 patients had detailed weight at the 3 time-points of assessment. The mean age at diagnosis was 51.8 years. The proportion of patients who received chemotherapy, radiotherapy and endocrine therapy were 77%, 70% and 72% respectively. Compared to T0, the median weight change was -0.5 kg (range: -11.4, 18.3) at T1 and 0 kg (range: -18.6, 19.5) at T2. At T1 and T2, 2.4% and 16.1% of women respectively gained weight between 2-5kg; 0.5% and 4.7% respectively gained >5kg, while 6.1% and 24.2% of women respectively had weight loss >2kg. On univariate analysis, patients who received radiotherapy had more weight loss at T1; no significant difference in weight change was noted with other factors including socio-demographic, lifestyle and clinical factors. When comparison was made between T0 and T2, patients who did not receive radiotherapy, those who remained premenopausal at T2 and those who were underweight at T0 were significantly associated with more weight gain.

Conclusions

In this cohort study, weight gain was not common among Hong Kong breast cancer patients within the first 18 months post-diagnosis. The findings from the present study differ from those conducted in western patient population, in whom average reported weight gains ranged between 1.0 and 6.0 kg over the first year after breast cancer diagnosis. Funding: World Cancer Research Fund International (Grant Number WCRF 2010/249 and WCRF 2014/1197).

Legal entity responsible for the study

Joint CUHK-NTEC Clinical Research Ethics Committee and the KWC Research Ethics Committee.

Funding

World Cancer Research Fund International (Grant Number WCRF 2010/249 and WCRF 2014/1197).

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

258P - Incidence of clinically significant toxicities in patients with high endoxifen concentrations

Presentation Number
258P
Lecture Time
12:45 - 12:45
Speakers
  • Steffie L. Groenland (Amsterdam, NL)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Tamoxifen is essential in the treatment of estrogen receptor positive breast cancer. Concentrations of its active metabolite endoxifen > 5.97 ng/mL have been associated with a 26% lower recurrence rate in the adjuvant setting (Madlensky 2011), providing a rationale for therapeutic drug monitoring. However, the risk of high endoxifen concentrations has not been established. Therefore, we investigated whether extremely high endoxifen levels are correlated with a higher incidence of clinically significant toxicities.

Methods

Patients receiving adjuvant tamoxifen treatment (20 mg) with a steady state endoxifen level above 25 ng/mL were retrospectively identified in databases of the CYPTAM study (n = 667, NTR 1509) and of samples collected in routine care (n = 1768). The percentage of patients with clinically significant toxicities, defined as toxicities leading to either dose reduction or treatment discontinuation, was compared to the overall tamoxifen population. As historical comparison, studies described in the EBCTCG overview (2011) in which patients received adjuvant tamoxifen (20 mg) and which reported clinically significant toxicities were selected.

Results

26 patients (1.5%) had an endoxifen level > 25 ng/mL, of which 4 patients (15%) had clinically significant toxicities, compared to 10.2% in the overall tamoxifen population (p = 0.39, weighed average of 10 clinical trials, n = 9688, Baum (2002), Margolese (2016), Chirgwin (2016), Morales (2007), Bartlett (1987), Colleoni (2006), Bonneterre (2001), Kaufmann (2005), Bramwell (2010), Tevaarwerk (2014)). Reported toxicities were mood disturbances (n = 3), hot flushes (n = 2) and musculoskeletal disorders (n = 1). Median time on treatment was 28 months in patients with high endoxifen levels, compared to 47 months reported in literature.

Conclusions

The incidence of clinically significant toxicities is relatively low and is similar in patients with extremely high endoxifen levels and the overall tamoxifen population. Therefore, dose reductions are not indicated in patients with high endoxifen concentrations without toxicity.

Clinical trial identification

CYPTAM study: NTR 1509 (release date 27 October 2008).

Legal entity responsible for the study

The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital.

Funding

Has not received any funding.

Editorial Acknowledgement

Not applicable

Disclosure

N. van Erp: Research funding (all to the institution): Novartis, Astellas, Janssen-Cilag, AstraZeneca, GSK, Boehringer-Ingelheim, Gilead, Roche, Pfizer, Sanofi. R.H.J. Mathijssen: Research support: Astellas, Bayer, Boehringer Ingelheim, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche and Sanofi; Consultation fees: Novartis, Servier; Travel Support: Astellas, Pfizer. N. Steeghs: Research funding (all to the institution): AstraZeneca, Bayer, BMS, Novartis, GSK, Pfizer, Roche, Boerringer Ingelheim, Blueprint. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

259P - Male Breast Cancer: Clinical and Epidemiological Patterns in the United States

Presentation Number
259P
Lecture Time
12:45 - 12:45
Speakers
  • Mohamed A. Gouda (Shebin El Kom, EG)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Male breast cancer is a rare disease that have different outcomes in comparison with the same disease in female counterparts. Due to rarity of its occurrence, data available on breast cancer in male population are relatively scarce. The aim of this study was to summarize data available in the SEER (National Cancer Institute Surveillance, Epidemiology, and End Results) program’s database about male breast cancer. SEER incorporates data from 18 cancer registries all over the United States. Data about clinical and epidemiological patterns as well as survival were analyzed and are subsequently presented.

Methods

Data were obtained using SEER*Stat version 8.3.5 where (SEER 18 Regs Nov 2017 Submission) database was used as the data source. Only males diagnosed between 2000-2015 with malignant breast cancer, known age, and microscopic confirmation were included. Relative survival was calculated using Ederer II method. Further data analysis was made using SPSS version 21.

Results

A total of 6790 patients were identified with a median age of 68. White race constituted the majority of cases (81.3%; n = 5519). Incidence rate was 10.2 per million (95% CI 10 – 10.5) with increasing trend over time (annual percent change = 1.9%, p < 0.05). The disease showed slight predilection to occur on the left side (52.3%; n = 3550). Most cases were staged as regional (n = 2974) or localized (n = 3152) at time of diagnosis. The disease was the only primary cancer in 4502 patients (66.3%) and the first of 2 or more primaries in 787 cases (11.6%). It occurred as a second or later multiple primary in remaining cases (22.1%). Median observed survival was 117.2 months with a 5-years and 10-years observed survival of 70.6% (CI: 69.1%-71.9%) and 48.8% (CI: 46.9%-50.6%) respectively. 5-years relative survival was 84% (CI: 82.3%-85.6%) while 10-years relative survival was 71.1% (CI: 68.3%-73.7%).

Conclusions

Male breast cancer is a rare tumor with an incidence rate of 10.2 per million. This tumor is more likely to occur in old age and white race and occurs more on left side. Disease occurred as a second (or later multiple) primary in 22% of cases. 5-years relative survival is 84% with a median survival of 117.2 months.

Legal entity responsible for the study

Mohamed Alaa Gouda.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

260P - The aesthetic results after oncoplastic surgery in early breast cancer

Presentation Number
260P
Lecture Time
12:45 - 12:45
Speakers
  • Aziz ZIKIRYAHODJAEV (Moscow, RU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

To create of the new concept of surgical treatment as a component of multi-therapy treatment of patients with breast cancers on postoperative quality of life (Qol). According to Clough K. B. (2010), the advantage of the oncoplastic approach is the expansion of indications for operations in achieving the best aesthetic results. "Oncoplastic surgery is the' third way ' between standard organ preservation surgery and mastectomy."

Methods

We assessed 570 women who underwent breast conserving surgery (BCS) or total mastectomy (TM) with immediate reconstruction in P.A. Gertsen Moscow Research Institute from 2013 to 2017. Of the 437 patients, 300 (66,4%) had oncoplastic breast surgery. OBS included glandular reshaping (rotation flap, round-block technique, batwing mastopexy, wise pattern-inverted T, vertical pattern). The distribution of patients according to the stage of disease was as following: stage I-II – 348 (79,6%), IIIA – 89 (22,4%). A median follow-up period was 58 months. Only 94 (21,5%) patients received adjuvant polychemotherapy, combinations adjuvant polychemotherapy and radiation therapy – 27 (6,1%) or endocrine therapy – 37(8,5%).

Results

During a median follow-up period local recurrent were detected at 5 (0,8%), distant metastasis – 15 (2,6%) patients. Overall disease-free survival in patients with BCS stage I was 96,2%, IIA– 90%, IIB – 86,7%, IIIA – 86,2% (p>0,05). Overall disease-free survival in patients with SSM stage I was 92,9%, IIA– 91,2%, IIB – 84,4%, IIIA – 91,4% (p>0,05). The postoperative cosmetic result after BCS was assessed in 79,3% patients.

Conclusions

In breast reconstructive the most effective method is using breast tissue after BCS. Oncoplastic surgery contributes is the better phychological adaptation of patients. Variety of modifications and options of reconstructive surgery causes problem of choice, which should be solved with patient taking into account the clinical data. The extent of surgical intervention does not affect the performance of the 5-year overall and recurrent survival and depends on the distribution process.

Legal entity responsible for the study

P.A. Gerzen's Cancer Research Institute – The National Medical Research Radiologic Center of the Ministry of Health of the Russian Federation.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

261P - The application of indocyanine green fluorescence navigation method to a sentinel lymph node biopsy after neoadjuvant chemotherapy in node-positive breast cancer

Presentation Number
261P
Lecture Time
12:45 - 12:45
Speakers
  • Kazuhiko Yamagami (Kobe, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Approximately 40% of patients with node positive in axilla (N1) will have axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). The application of sentinel lymph nodes (SNs) biopsy (SNB) following NAC for initially node-positive breast cancer is unclear because of high false-negative results in previous studies (SENTINA, ACOSOG Z1071). These trials, using blue dye (BD) and/or radioisotope (RI) agent, showed the diagnostic accuracy of SNB was closely related to the number of SNs. We presented the efficacy of indocyanine green (ICG) fluorescence navigation method for SNB in clinically node-negative (cN0) patients (ASCO2008). The fluorescent ICG method can provide higher number of SNs. Moreover, some reports showed that florescence SNs with metastases could not be identified by radioactivity. To determine the detection rate, the false-negative rate of SNs using the fluorescent ICG method after NAC for biopsy-proved N1 breast cancer retrospectively.

Methods

Of 2301 patients (January 2010 - March 2018), 135 women with N1 (fine needle aspiration or core needle biopsy proved) received NAC. Node status after NAC was evaluated by ultrasound findings: Group 1 (N1 converted ycN0, n = 105) and Group 2 (N1 remained ycN1, n = 30). All patients underwent SNB using both ICG- and BD-method and axillary lymph node dissection.

Results

The average number of SNs removed were Group 1 (ICG: 3.65, BD: 1.37), Group 2 (ICG: 2.99, BD: 0.93). Detection rate of SNs: Group 1 ICG 97.1% (95% CI 91.9-99.0, 102 of 105), BD 77.1% (95% CI 68.2-84.1, 81 of 105), Group 2 ICG 86.7% (95% CI 70.3-94.7, 26 of 30), BD 53.3% (95% CI 36.1-69.8, 16 of 30). Resulting of a false-negative rate: Group 1 ICG 7.69% (95% CI 2.65-20.3, 3 of 39), BD 35.7% (95% CI 20.7-54.2, 10 of 28), Group 2 ICG 11.5% (95% CI 4.00-29.0, 3 of 26), BD 18.8% (95% CI 6.59-43.0, 3 of 16). Axillary pCR was 46.7% (63 of 135).

Conclusions

In patients whose axillary nodal status converted from N1 to ycN0, the fluorescent ICG method with higher number detection of SNs showed a remarkable high detection rate and a low false-negative rate of SNs, compared with those of Blue dye which is one of conventional method.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

262P - Use of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Patients with Cytology Proven Axillary Node-Positive Breast Cancer at Diagnosis

Presentation Number
262P
Lecture Time
12:45 - 12:45
Speakers
  • Hee Jun Choi (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

This study aimed to evaluate the prognostic effects of sentinel lymph node biopsy (SLNB) on recurrence and survival after neoadjuvant chemotherapy (NAC) in patients with cytology-proven axillary node metastasis breast cancer.

Methods

This study is a registered medical record review based on a prospectively collected cohort. We selected 506 patients who were diagnosed with invasive breast cancer and axillary lymph nodes metastasis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2014. We classified patients into three groups: Group A, negative SLN status and no further dissection; Group B, negative SLN status with backup axillary lymph node dissection (ALND); and Group C, no residual axillary metastasis on pathology with ALND regardless of clinical response. We analyzed and compared outcomes including prognoses and survival among all groups.

Results

The median age at the time of surgery was 44.4 years. The median follow-up time was 47.0 months (range: 3-115 months) and the median number of retrieved SLNs was 5.0. The SLN identification rate was 98.3% (234/238 patients), and the false negative rate (FNR) of SLNB after NAC was 7.5% (8/106 patients). There was no significant difference in disease-free survival (DFS, p = 0.578) or overall survival (OS, p = 0.149) among Groups A, B, and C.

Conclusions

These results suggest that SLNB can be feasible and oncologically safe after NAC for node-positive breast cancer and could help reduce arm morbidity by avoiding standard ALND in negative SLN patients.

Legal entity responsible for the study

Samsung Medical Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

263P - Omission of Axillary Lymph Node Dissection after Positive Sentinel Lymph Node: Validity and Safety among Early Breast Cancer Patients Treated with Mastectomy

Presentation Number
263P
Lecture Time
12:45 - 12:45
Speakers
  • Akiko Matsumoto (Tokyo, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

ACOSOG Z0011 trial showed that axillary lymph node dissection (ALND) had no impact on recurrence and survival in patients with positive sentinel lymph node (SLN) after breast-conserving surgery. However, it is still unknown if omission of ALND can be applicable to patients treated with mastectomy. The aim of this study was to evaluate whether ALND could be safely omitted for patients with SLN–positive breast cancer after mastectomy.

Methods

From a prospective database of 296 patients with clinically node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy (SLNB) from March 2006 to December 2016, 81 patients who had positive SLNs were analyzed. Patients treated with neoadjuvant chemotherapy were excluded from the analysis. Lymphatic mapping was performed with a combined method of blue dye and radioisotope.

Results

The median age was 57.0 (range: 32-85) years and the median tumor size was 2.5 (range: 0.6-7.9) cm. Of 81 patients, 23 (28.4%) patients omitted ALND. Patients with SLNB alone were more likely to have smaller SLN involvements (p < 0.001): micrometastasis was identified in 13 (56.5%) patients in SLNB-alone group and 9 (15.5%) patients in ALND group. The number of positive SLN was comparable between SLNB-alone (median: 1.0, range: 1-6) and ALND groups (median: 1.0, range: 1-5) (p = 0.063). There was no significant difference in characteristics including age, tumor size and tumor subtypes between the two groups. Post-mastectomy radiotherapy was performed in 5 (21.7%) patients with SLNB alone and 16 (27.6%) patients with ALND (p = 0.588). The majority of patients with macrometastatic SLN received adjuvant chemotherapy in both groups (83.3% vs. 75.5%, p = 0.562). After a median follow-up of 54.7 months, no axillary recurrence was observed in both groups and 5-year disease-free survival was not significantly different between the two groups (75.0% vs. 88.8%, p = 0.489). Lymphedema was observed significantly more often after ALND than after SLNB (22.4% vs. 4.3%, p = 0.045).

Conclusions

These data suggested that ALND could be safely omitted in SLN-positive breast cancer patients treated with mastectomy and appropriate systemic therapy.

Legal entity responsible for the study

Akiko Matsumoto.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

264P - Pathologic response as a strong predictor of survival irrespective of phenotype in early Breast Cancer

Presentation Number
264P
Lecture Time
12:45 - 12:45
Speakers
  • Ariadna Gasol Cudos (Lleida, ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Pathologic complete response after neoadjuvant chemotherapy is considered as a surrogate of survival by most authors, although there are special phenotypes, such HER2 positive, where their potential as apredictor of survival is stronger.

Methods

Overall survival was analyzed according to pathologic response in a cohort of early breast cancer patients (all subtypes) treated with standard neoadjuvant chemotherapy. Between March 2000 to October 2016, 459 breast cancer patients were treated with neoadjuvant chemotherapy with anthracicline and taxane regimens.

Results

Median age was 52 (range 28-87), 173 tumors (38%) were classifyed as HER2 positive, 148 (32%) triple negative and 138 (30%) as luminal breast cancer. Median initial size was 34 mm (10-100) and 237 patients (51%) had initial node involvement. We achieved a total of 152/459 complete pathologic response with a 43% rate in HER2 positive, 44% in triple negative and 9% in luminal breast cancer patientes. Ten years disease free survival in the whole serie was 83%, with a 72% for patients without complete pathologic response versus 90% for complete pathologic response (long rang <0,00001). A strong correlation between pathologic response and survival wass found in all subtypes (long rang p:0,033; 0,028 and 0,027 in HER2 positive, luminal and triple negative respectively). A table with survival results according the RCB response by Symmans method in the whole series and different phenotypes is attached.

PhenotypeRCB type 0RCB1 type IRCB type IIRCB type III
OverallMedian DFS:167 HR: 1Median DFS:156 HR: 2,6Median DFS:130 HR: 4,5Median DFS:85 HR: 9,6
HER 2 positiveMedian DFS: 126 HR: 1Median DFS: 90 HR: 1,6Median DFS:100 HR: 2,5Median DFS:96 HR: 4,4
LuminalMedian DFS: 176 HR: 1Median DFS: 160 HR: 2,8Median DFS:115 HR: 4,8Median DFS: NA HR: NA
Triple negativeMedian DFS:188 HR: 1Median DFS: 141 HR: 8,8Median DFS: 117 HR: 16,7Median DFS:122 HR: 28.4

Conclusions

Pathologic response is a strong predictor of overall survival in all breast cancer phenotypes althoug in the triple negative has the highest magnitude with a HR of 28,4 in patients with worse pathologic response (RCB type III). Neoadjuvant chemotherapy should be considered in the majority of patients who are candidates to chemotherapy, specially in triple negative and HER2 positive; however, in luminal phenotype a better selection for neoadyuvant chemotherapy is needed.

Legal entity responsible for the study

Hospital Universitari Arnau de Vilanova.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

265P - Nomogram to predict non-sentinel lymph node status of breast cancer using total tumor load determined by one-step nucleic acid amplification (OSNA)

Presentation Number
265P
Lecture Time
12:45 - 12:45
Speakers
  • Pornchai O-charoenrat (Bangkok, TH)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Axillary dissection might be omitted in selected breast cancer patients with positive sentinel node (SLN). Total tumor load (TTL) in SLN expressed by cytokeratin 19 (CK19) mRNA, detected by automated molecular technique-one-step nucleic acid amplification (OSNA), can quantitatively determine tumor burden in SLN. This study aimed to create nomogram to predict non-sentinel lymph node (NSLN) status.

Methods

Breast cancer patients were recruited at Division of Head Neck and Breast Surgery, Department of Surgery, Siriraj Hospital, Mahidol University, Thailand from November 2015 to January 2018. The patients with invasive breast cancer T1-T3, clinically negative axillary lymph node and able to give informed consent underwent SLN biopsy assessed by OSNA. The patients with positive SLN underwent axillary lymph node dissection. Correlations between TTL, clinicopathological parameters and NSLN status were analyzed by chi-square statistic and logistic regression. Model discrimination was evaluated using receiver-operating characteristic (ROC) analysis.

Results

Total number of the patients who underwent SLN biopsy was 262. There were 85 patients with positive SLN. Mean age at diagnosis of the patients in this group was 54.52±11.66 years. NSLNs were positive in 37 patients. Larger tumor size (25.35±9.02 mm vs 37.78±16.88 mm) and presence of lymphovascular invasion (24.5% vs 67.6%) were the independent factor that predict positive NSLN. TTL expressed by CK19 mRNA copy number can discriminate NSLN status with the area under ROC curve of 0.784 (95%CI 0.683-0.885). At the cut off level at 6550 copies/μL, sensitivity, specificity, and negative predictive value were 86.49%, 57.14%, and 84.85%, respectively. Nomogram containing tumor size and SLN status can predict NSLN involvement with area under ROC curve of 0.827 (95%CI 0.737-0.918).

Conclusions

Nomogram using the results by OSNA technique can predict NSLN status and help in decision for axillary lymph node dissection.

Legal entity responsible for the study

Pornchai O-charoenrat.

Funding

Sysmex.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

266P - Detecting Bone Density in Early Breast Cancer Survivors: The Arm-DXA method

Presentation Number
266P
Lecture Time
12:45 - 12:45
Speakers
  • Yousuf Al-Farhat (Szeksyard, HU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Breast cancer survivors who are on adjunct therapy with Aromatase Inhibitors (AIs) or premature menopause due to chemotherapy are known to have an increased risk of osteoporosis and bone fracture. Being at high risk for osteoporosis, these patients should be screened using with dual energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD) according to national guidelines. This study screened the population of patients with early Breast cancer utilizing the Arm-DXA as a user friendly and efficient method.

Methods

All Breast cancer patients at the Tolna County Cancer Center, Szekszárd who are diagnosis of early invasive breast cancer were scanned using Arm-DXA during their regular visit to the center. Cancer patients under hormone therapy were scanned annually. Patients who have metastatic disease or known to have osteoporosis were excluded from the study. A total of 431 patients were subject of an arm-DEXA scan for BMD during the period February 2015 to September 2017.

Results

Out of the 431 patients, normal T score −1,5 detected in 223 patients (51,7%), clinically significant osteopenia (CSO) T score −1,5, −2,5 detected in 129 patients (29,9%), and osteoporosis T score < −2,5 detected in 79 patients (18,3%). For the 224 Patients who were under hormone therapy or/and chemotherapy about 29,9% (n: 67) had a CSO, and 20,5% (n:46) had osteoporosis.

Conclusions

This study highlights the fact that osteoporosis is under-detected in early breast cancer survivors who are on or after hormone and chemotherapy. About 48% of early breast cancer survivors found to have osteoporosis or clinically significant osteopenia in our study. Our BMD test results shows that half the 224 patients who were under hormone therapy need to take treatment (zoledronic -acid or denosumab) to prevent bone fracture.

Legal entity responsible for the study

Al-Farhat Yousuf.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

267P - Voluntary deep inspiration breathhold (DIBH) experience in the radiotherapy for left sided breast cancer

Presentation Number
267P
Lecture Time
12:45 - 12:45
Speakers
  • Ivan V. Gueorguiev (Sofia, BG)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The adjuvant radiotherapy to the whole breast or the chest wall is an integral part of the treatment of breast cancer. This study is aimed at evaluating the potential for sparing the heart and lung using voluntary deep inspiratory breath-hold (DIBH) technique for radiotherapy of left sided breast or chest wall.

Methods

During the period 09.2016 – 09.2017, 95 patients with breast cancer had planning CT scans in the both respiratory phases, using Varian Real Time Positioning Management System® for monitoring of the respiratory chest wall excursions. Each patient had two planning CT scans: one during free breathing (FB) and another one with voluntary deep inspiration breath-hold (DIBH). The Planning Target Volume (PTV) included the whole breast/chest wall with or without the supraclavicular nodal groups (SCL). For each patient, two radiotherapy plans were prepared using the FB and the DIBH planning scans.

Results

The DIBH was very well tolerated. The mean anterior-posterior chest wall shift during FB was 3.1 mm. With the DIBH, the front chest wall position was between 10 mm and 18 mm anteriorly to its mid-FB position. In the post-lumpectomy cases the portion of the heart that received more than 50% of the prescribed dose, was decreased from 2.07% to 0% (39.7 % max dose). At the same time, relative lung volume irradiated to > 50% of the prescribed target dose was reduced from 17.63% (for FB) to 13.2% (for DIBH). In one extreme case with SCL, the volume of the heart, receiving more than 50% of the prescribed dose, was: 5.74% for FB and 0% for DIBH (36% max dose); the ipsilateral lung received: 21.2% with FB and 8% with DIBH. The median ipsilateral relative lung volume receiving >50% was higher for DIBH – 14.17% and 10.91% for FB.

Conclusions

This is the first study in Bulgaria, which demonstrates the dosimetric benefits of breathing adapted radiotherapy (BART). Our results showed that irradiated cardiac volumes can be consistently reduced for left-sided breast cancers by using DIBH.

Legal entity responsible for the study

Ivan Gueorguiev.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

268P - Psychological distress and health-related quality of life in women recently diagnosed with breast cancer in the Epi-GEICAM study.

Presentation Number
268P
Lecture Time
12:45 - 12:45
Speakers
  • Nerea , Fernández-De-Larrea (Madrid, Alcalá de Henares., ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Breast cancer (BC) diagnosis may have a high emotional impact in patients. Health-related quality of life (HRQL) can be impaired by the psychological impact of the diagnosis, by choices having to be made about treatment and by treatments themselves.

Methods

Cross-sectional analysis of HRQL in BC women from the Epi-GEICAM case-control study carried out in 23 Spanish hospitals. Women fulfilled a questionnaire about sociodemographic and lifestyle factors, HRQL (SF-36), mental health (GHQ-28) and social support (Duke-UNC). Spanish population norm-based scores were calculated for the SF-36 scales. Physical (PSS) and mental (MSS) summary scores ≥5 points under the norm were considered suboptimal. Psychological distress (PD) was defined as GHQ-28 >5. Factors associated with PD and suboptimal PSS were identified by multivariable mixed logistic regression models.

Results

Among 1017 cases, 896 had complete SF-36 and GHQ-28. Median time since diagnosis was 77 days, 82% had been operated on, and 41% were on radiation/chemotherapy. Prevalence of PD was 54.4% (95% CI: 51.1-57.6). PD increased with TNM stage (p = 0.03). Other factors associated with PD were chemotherapy (OR = 1.7; 95% CI: 1.2-2.6), low social support (OR = 2.0; 95%CI: 1.2-3.5) and low education (OR = 2.1; 95% CI: 1.2-3.8). SF-36 scores are described in the table. Factors related to suboptimal PSS were surgery (OR = 3.2, 95% CI: 2.0-5.1), low education (OR = 1.9, 95% CI: 1.1-3.6) and number of comorbidities (OR = 1.3, 95% CI: 1.0-1.5). No differences in PD or PSS were observed according to BC subtype.

Conclusions

PD is very frequent during the initial stages of BC diagnosis and treatment. Advanced disease stage, lack of social support and low education are strong determinants of PD. The highest impact in HRQL was observed in the role-physical domain. PD and low PSS are interrelated and both are more frequent in patients with low education.

Mean*95% CI
Physical function41.240.342.1
Role physical36.836.037.5
Bodily pain45.044.445.7
General health46.946.247.5
Vitality46.846.147.5
Social function41.340.442.1
Role emotional44.643.845.5
Mental health46.746.147.4

<50: under the norm

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group.

Funding

GEICAM Spanish Breast Cancer Group.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

232TiP - A multicentre, international neoadjuvant, double-blind, randomized phase III trial comparing fulvestrant to a combination of fulvestrant and palbociclib (CDK 4/6 inhibitor) in patients with operable luminal breast cancer responding to fulvestrant (SAFIA study).

Presentation Number
232TiP
Lecture Time
12:45 - 12:45
Speakers
  • Jean-Marc Nabholtz (Riyadh, SA)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Neo-adjuvant (NA) chemotherapy (CT) +/- anti-Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in hormonal receptor+/Her2 negative BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs (i.e. 5% using 8 months of ET).

Trial design

This is a multicenter phase III, 3rd generation neo-adjuvant trial performed in 34 centers and 8 countries of Middle-East and Maghreb with the objective to investigate the potential role of the addition of a CDK 4/6 inhibitor (Palbociclib) to ET (Fulvestrant+/- Goseriline) compared to ET alone as neo-adjuvant therapy of HR+/ Her2- operable BC sensitive to ET. The question Is whether or not ET plus CDK 4/6 inhibitor would yield high enough pCR rates to establish this strategy as a reasonable therapeutic option in this group of patients (pts) with luminal HER2- BC. A total of 400 pts with stage II and IIIA are planned to be recruited in this trial. Oncotype DX will be performed upfront in order to eliminate CT candidates. All pre/peri and post-menopausal pts with a recurrence score < 31 will be treated with 4 months of Fulvestrant (500 mg Day (d.) 1, 14, 28 then q. 28 d. (+/- Goseriline 3.6 mg q.28 d.). Patients with responding/stable disease will then be randomized in double blind fashion to Fulvestrant (+/- Goseriline) either with Palbociclib 125mg po daily 3 weeks/4 or placebo. Four additional cycles will be delivered before surgery. The study primary endpoint is pCR while clinical/radiological response, rate of conservative surgery, safety, disease-free and overall survival are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies. The SAFIA trial aims to identify a new neo-adjuvant standard with ET plus CDK 4/6 inhibitor in luminal - Her2 negative operable BC.

Clinical trial identification

SAFIA Study (ICRG 1201); NCT03447132.

Legal entity responsible for the study

International Cancer Research Group (ICRG).

Funding

AstraZeneca, Pfizer and Genomic Health.

Editorial Acknowledgement

not applicable

Disclosure

J-M. Nabholtz, F. Dabouz, S. Kullab: Research grants: AstraZeneca, Pfizer, Genomic Health. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

269TiP - Multicenter study to evaluate the efficacy and standardize radiofrequency ablation therapy for early breast cancer (RAFAELO study)

Presentation Number
269TiP
Lecture Time
12:45 - 12:45
Speakers
  • Takayuki Kinoshita (Tokyo, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Given the increasing number of early-stage breast cancers detected by screening mammography, we aim to establish RFA as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically.

Trial design

The objective of our study is to demonstrate the non-inferiority of RFA compared with standard treatment in terms of local recurrence-free survival, which is the best index of local control. The inclusion criteria are untreated pts with histologically confirmed ductal carcinoma with a single localized tumor of 1.5 cm or less in the greatest dimension on preoperative imaging, no prior treatment for breast cancer.

RFA is defined as a procedure in which a radiofrequency electrode needle is inserted into the breast lesion from the surface of the body under imaging guidance and thermal ablation with radiofrequency waves is performed. The Cool-tip™ RF Ablation Single Electrode Kit (Medtronic, Boulder, CO, USA) is recommended to standardize the evaluation of the effect of ablation. All pts receive RT and systemic therapy according to the ER, HER2, tumor grade and lymph node status of the primary breast cancer after RFA. Residual lesions after RFA will be assessed in all patients approximately 3 months after RT using imaging studies and pathological examination. VAB will be performed in all patients regardless of imaging results. If biopsy specimens reveals suspicious of viable tumor, additional excision will be performed. Follow-up evaluation for residual tumor every 12 months after RFA included clinical breast examination, diagnostic imagings (ultrasound, magnetic resonance, and mammography). The primary endpoint is 5-year local recurrence-free survival, and the secondary endpoints are residual lesion rate after treatment, overall survival, distant recurrence-free survival and adverse events of RFA. The pts accrual was started in August 2013. From 9 participating institutions, enrollment of 372 pts is planned over a 5-year accrual period.

Clinical trial identification

UMIN-CTR: UMIN000005586.

Legal entity responsible for the study

Takayuki Kinoshita.

Funding

The Japan Agency for Medical Research and Development.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

270TiP - Mutanome engineered RNA immuno-therapy (MERIT) for patients with triple negative breast cancer (TNBC)

Presentation Number
270TiP
Lecture Time
12:45 - 12:45
Speakers
  • Ludwig Heesen (Mainz, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Treatment of triple negative breast cancer (TNBC) is hampered by lack of established therapeutic targets like hormone receptors or HER-2. Surgery, chemotherapy and radiotherapy are the standard of care yet cure rates in patients with TNBC remain inferior compared to other BC subtypes. Approaches tailored to the patient’s individual tumor signature may lead to improvement. The “Mutanome Engineered RNA Immuno-Therapy (MERIT)” consortium is validating an innovative individualized mRNA-based vaccine for TNBC treatment. MERIT is a collaboration of 5 European partners (academia and industry) dedicated to realize a personalized approach for TNBC treatment. The consortium set up a clinical workflow covering drug development from target discovery and validation to GMP manufacturing and drug release for each individual patient (MUTANOME). Moreover, the consortium established a pre-synthesized mRNA vaccine warehouse containing the most frequently shared tumor-associated antigens (TAA) in TNBC for drug supply (WAREHOUSE).

Trial design

A phase I trial in 2 European countries assesses the feasibility, safety and biological efficacy of this personalized immunotherapy. TNBC patients (pT1cN0M0 – TxNxM0) after surgery and (neo-)adjuvant chemotherapy will be allocated to one of two study arms. Patients in ARM1 receive 8 WAREHOUSE vaccinations with personalized TAA combinations corresponding to the patient tumor’s antigen-expression profile. Patients in ARM2 are first treated with the WAREHOUSE approach followed by 8 vaccination cycles of an on-demand manufactured MUTANOME vaccine encoding the unique mutation signature of the individual patient identified by NGS. The mRNAs are administered intravenously as a RNA-lipoplex formulation which protects RNA from degradation, activates innate immunity, transfects APCs and consequently induces highly potent antigen-specific T-cell responses. Three clinical sites are open for recruitment; >12 patients were screened and vaccinations with WAREHOUSE or MUTANOME RNAs have started. We give insights into features of the established process and present first stratification data. MERIT was funded by the EU Commission’s FP7 and is led by BioNTech AG.

Clinical trial identification

EudraCT: 2014-002274-37.

Legal entity responsible for the study

BioNTech AG.

Funding

European Commission’s FP7; BioNTech AG.

Disclosure

L. Heesen, K. Frenzel, S. Bolte, V. Bukur, E. Derhovanessian, S. Kreiter, A. Kuhn: Employment: BioNTech. M. Diken: Patent ownership, patent applications, employment: BioNTech AG. K. Kühlcke: Employment: BioNTech IMFS. T. Sjöblom: Founder, board member, shareholder: ExScale Biopecimen Solutions. A. Ö. Türeci: Co-founder: Ganymed Pharmaceuticals GmbH. U. Sahin: Patent ownership, patent applications, stock owner, management board member, co-founder: BioNTech AG; Co-founder, chair: TRON gGmbH; Membership on advisory board, co-founder: Ganymed Pharmaceuticals GmbH. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

271TiP - Preoperative Pembrolizumab (Pembro) with Radiation Therapy (RT) in Patients with Operable Triple-Negative Breast Cancer (TNBC)

Presentation Number
271TiP
Lecture Time
12:45 - 12:45
Speakers
  • Heather L. McArthur (Los Angeles, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Radiation therapy (RT) induces immune-mediated cell death. If administered pre-operatively, RT could also generate a rich supply of tumor antigens. The addition of PD-1 mediated checkpoint blockade to pre-operative RT could thus, generate robust anti-tumor immune responses, induce long-term tumor-specific memory, and ultimately, improve cure rates. This study aims to establish the safety of pre-operative pembrolizumab (pembro)-mediated immune modulation with a RT “boost” equivalent in patients with operable triple negative breast cancer (TNBC) for whom lumpectomy and adjuvant RT are planned (NCT03366844). Serial research biopsies will permit interrogation of conventional biomarkers including tumor infiltrating lymphocytes (TILs) and novel immune correlates as potential predictors of response to pembro alone versus pembro with RT.

Trial design

Women with operable, primary TNBC >2cm for whom breast-conserving therapy is planned are enrolled in this single-institution pilot study. Study treatment consists of 1 cycle of pre-operative pembro (200 mg IV) alone, followed 3 weeks later by a RT boost (24 Gy/3 fractions) to the primary breast tumor concurrently with pembro (+/- 5 days). Curative-intent, standard-of-care, neoadjuvant chemotherapy or breast-conserving surgery is then undertaken within 8 weeks of study enrollment (i.e. within 5 weeks of pembro #2). Adjuvant RT is administered per standard-of-care after surgery, but without a boost dose. Research blood and fresh tumor biopsies are obtained at baseline and after cycles 1 and 2 of pembro. Correlative analysis will include single-cell RNA sequencing of the tumor immune infiltrate and multispectral immunohistochemistry. Co-primary endpoints are: 1) safety/tolerability, as defined by the number of patients who do not necessitate a delay in standard-of-care chemotherapy or surgery and 2) change in TIL score. Secondary endpoints include safety/toxicity up to 19 weeks after study enrollment and disease-free survival.

Legal entity responsible for the study

Heather McArthur.

Funding

Has not received any funding.

Disclosure

H.L. McArthur: Advisory boards: Amgen, Celgene, Immunomedics, Merck, OBI Pharma, Pfizer, Puma, Spectrum Pharmaceuticals, Syndax Pharmaceuticals, Roche, Peregrine, Calithera, Eli Lilly, TapImmune; Research support: Bristol-Myers Squibb, Eli Lilly, MedImmune, LLC/AstraZeneca, Merck. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

272TiP - Development of mPRO Mamma mobile application and its impact on the quality of life and health resource usage in patients with early stage and locally advanced breast cancer receiving chemotherapy

Presentation Number
272TiP
Lecture Time
12:45 - 12:45
Speakers
  • Tjasa Gortnar (Ljubljana, SI)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Many possible adverse effects, from mild to life threatening, accompany the systemic treatment of cancer patients. Recognition and appropriate action is essential for optimal quality of life of patients. Consequently, patient-reported outcomes have become essential in clinical oncology. The purpose of this study is to involve the patients in ongoing monitoring, recording, and resolution of adverse effects resulting from chemotherapy via a self-developed smartphone application. We aim to assess the effect of this mobile application on improving symptom management and optimising health care usage, thus positively affecting the quality of life of our patients.

Trial design

We plan to develop a mobile application mPRO Mamma, which includes: symptom reporting module, useful measures and tips for managing adverse events based on intensity of symptoms, cancer-specific educational materials and an option to share collected data with the oncologist. Between December 2017 and June 2018, we plan to enrol 90 patients with early-stage or locally advanced breast cancer who own an Android-based smartphone and are proficient in using mobile applications in the open trial prior to them starting chemotherapy. Pending completion of mPRO Mamma mobile app development, half of the patients will be assigned to the control group. Upon the release of mPRO Mamma, the other half of the patients will be assigned to the experimental group and given access to the app. The primary objective is to determine the effect of using mPRO Mamma on the quality of life, measured by self-report using EORTC QLQ - BR23 and EORTC QLQ-C30 (version 3.0). Assessment will be performed before the first cycle, after 1 week, at the end of the first cycle, and at the end of chemotherapy. The quality of life index scores in each group will be compared to baseline scores. The secondary objectives are to assess the usage of health resources and to build a database of incidences of adverse events related to chemotherapy for breast cancer.

Clinical trial identification

EudraCT: 2018-001869-16.

Legal entity responsible for the study

Institute of Oncology Ljubljana, Slovenia.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

Breast cancer, locally advanced

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

274P - CD8+, CD4+ and FOXP3+ cell profiles and their change after neoadjuvant chemotherapy in patients with triple negative breast cancer

Presentation Number
274P
Lecture Time
12:45 - 12:45
Speakers
  • Nataliia O. Verovkina (Kiev, UA)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Neoadjuvant therapy for breast cancer has been increasingly used in recent years as first-line treatments for breast cancer. A high lymphocytic infiltration is known to correlate with response to neoadjuvant chemotherapy and prognosis, however little attention has been paid to changes in CD8+, CD4+, FOXP3+ immune call profiles during perioperative chemotherapy.

Methods

Treatment results of 43 patients with TNBC stages IIB-IIIB homogeneously treated with neoadjuvant chemotherapy were analyzed. We studied the baseline and post-treatment FOXP3+, CD4+, CD8+ tumor-infiltrating immune cells by immunohistochemistry. Therapeutic pathomorphism was evaluated in terms of the residual tumor burden identification (RCB) (using Miller-Payne classification). Variables distribution was scored using ANOVA test. Survival probabilities were estimated by the Kaplan-Meir method. Hazard ratios and their 95% confidence interval were calculated with the Cox proportional hazards model.

Results

Pathological complete response (pCR) to neoadjuvant chemotherapy was identified in 12% of patients. In group without pCR high baseline levels of the stromal CD4+ cells were identified in 39,4% of patients, peritumoral CD4+ cells – in 44,7%; high levels of stromal CD8+ cells were identified in 28% and peritumoral CD8+ – in 52% of patients; and high levels of FOXP3+ were identified 47,3% of patients. The levels of CD8+ and FOP3+ cells decreased during treatment in 13% of patients. The levels of peritumoral CD4+ cells deceased during treatment in 34, % of patient, whereas levels of stromal CD4+ increased during treatment in 10,6% of patients. We found that in the population with residual disease after neoadjuvant chemotherapy the high baseline levels of peritumoral CD4+ immune cells were strongly associated with adverse outcome (HR 3,33, CI 1,29 – 8,58; p = 0,013).

Conclusions

The high baseline levels of peritumoral CD4+ lymphocytes in triple negative breast cancer tumor failing to achieve pCR were associated with adverse outcome. Further studies are required for identifying patients who are likely to benefit from immunotherapeutic adjuvants to conventional treatment approaches.

Legal entity responsible for the study

National Cancer Institute, Ukraine, Kiev.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

275P - Multiplex immunoassays analysis of plasma biomarker levels and response to neoadjuvant chemotherapy for locally advanced breast cancer

Presentation Number
275P
Lecture Time
12:45 - 12:45
Speakers
  • Jang Ho Cho (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Neoadjuvant chemotherapy (NAC) has become as the preferred initial therapy for locally advanced breast cancer (LABC) patients. A pathologic complete response (pCR) following NAC correlates strongly with both prolonged disease-free survival and overall survival especially for patients with HER2+ or triple negative breast cancer (TNBC). A lot of modalities and molecular markers for assessing chemotherapy response have been evaluated; however, they have demonstrated only limited predictive value.

Methods

Plasma samples have been collected from 167 patients diagnosed with LABC and received NAC from month, year to month, year prospectively. Samples were collected three times from each patient, prior to NAC (pre-treatment), prior to second cycle of NAC (on-treatment), and after breast surgery (post-treatment). Samples were assayed by multiplex immunoassays for 45 biomarkers. Plasma biomarker levels using Cytokine/Chemokine/Growth Factor 45-Plex Human ProcartaPlexTM Panel were compared with pathologic treatment responses. pCR was defined as the absence of residual tumor both in breast and axillary lymph nodes. This study was approved by the Institutional Review Board of Samsung Medical Center (SMC 2014-11-015-017).

Results

A median age at diagnosis of the 167 patients was 42 (range, 23-68 years). Most of the patients were treated with anthracycline and taxane-based regimen including adriamycin with cyclophosphamide plus docetaxel (AC-T), or AC-T plus trastuzumab. The patients were divided into the following four groups: HR+/HER2- (n = 46, 28%), HR+/HER2 + (n = 26, 16%), HR-/HER2 + (n = 32, 19%), and TNBC (n = 63, 38%). Thirty four patients (20%) achieving a pCR were compared with 133 patients (80%) demonstrating no pCR. Several groups of biomarker expression, BDNF, bNGF, HGF, IFN-gamma, IL-18, IP-10, MCP-1, RANTES, and SCF, were significantly different among pre-treatment, on-treatment and post-treatment. Multivariate analysis on pCR showed that analysis using the multiplex panel has predictive power.

Conclusions

Plasma biomarkers including immune-cytokine may have a role to predict treatment response in the neoadjuvant setting.

Legal entity responsible for the study

Samsung Medical Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

276P - Prognostic role of changes in neutrophil-to-lymphocyte ratio, tumor-infiltrating lymphocyte with programmed death ligand-1 in triple-negative breast cancer

Presentation Number
276P
Lecture Time
12:45 - 12:45
Speakers
  • Eun Kyo Joung (Seoul, KR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Neutrophil-to-lymphocyte ratio (NLR), tumor-infiltrating lymphocyte (TIL) and programmed death-ligand 1 (PD-L1) expression is known to be associated with immunogenicity and prognosis of breast cancer. We analyzed baseline NLR and its clinical association in triple-negative breast cancer (TNBC). The changes of NLR, TIL and PD-L1 during neoadjuvant chemotherapy (NAC) and their association to recurrence was analyzed.

Methods

Between Jan 2008 to Dec 2015, 358 TNBC patients were analyzed. NLR was based on initial complete blood count (CBC). Fifty paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen) were collected. The changes of TIL, CD4, CD8, forkhead box P3 (FOXP3) and PD-L1 expression were assessed with immunohistochemical stain. The relationship of prior markers and tumor recurrence was analyzed.

Results

Low NLR (NLR≤3.16) was associated to superior survival [overall survival; 41.83 vs. 36.5 months, P = 0.002; disease-free survival (DFS) 37.85 vs. 32.14 months, P = 0.032]. After NAC, patients with radical NLR changes (NLR change < -30% or > 100%) showed inferior DFS (38.37 vs. 22.37 months, P = 0.015). Same or increased TIL after NAC showed trends for superior DFS (80.0 vs. 46.0 months, P = 0.366). Positive PD-L1 (≥1%) in tumor cells at baseline was associated to superior DFS (97.45 vs. 33.02 months, P = 0.031), and positive tumor PD-L1 at post-NAC tissues showed trends for superior DFS (86.43 vs. 38.76 months, P = 0.056).

Conclusions

In TNBC patients, low NLR might be associated with superior survival. Modest changes of NLR or increased TIL after NAC may reflect good prognosis. Positive tumor PD-L1 was associated with superior DFS in our study.

Legal entity responsible for the study

Seoul St. Mary's Hospital, Incheon St. Mary's Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

277P - Expression of Sp17 and its association with clinicopathological parameters of breast cancer

Presentation Number
277P
Lecture Time
12:45 - 12:45
Speakers
  • Yu-ting Zhou (Chengdu, CN)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Sperm protein 17 (Sp17) was found to be only expressed in breast cancer and not the normal breast tissue. Although Sp17 antibody can effectively inhibit the growth of human cancer cells, suggesting a potential therapeutic target, the role of Sp17 in tumor remains unclear. Hence, we examined the expression status of Sp17 in breast cancer and analyzed the correlation between Sp17 expression and clinicopathological parameters of breast cancer. We then proceeded to assess whether the expression of Sp17 has any effect on patient prognosis.

Methods

Quantitative real-time PCR and immunohistochemistry were conducted to test expression rate of Sp17 mRNA and protein in breast cancer samples, respectively. Clinicopathological parameters of each patient were collected by reviewing medical records. Reliable follow-up information was obtained via phone call. Kaplan–Meier regression was conducted for survival analysis. Univariate and multivariate analyses were used to identify the variables associated with Sp17 expression.

Results

We studied 100 primary breast cancer and 20 normal breast specimens. Sp17 was expressed in 27% of breast cancer samples. The difference between expression and non-expression of Sp17 was statistically significant in disease-free survival and overall survival. Lymph node metastasis and molecular subtyping were independent factors associated with Sp17 expression.

Conclusions

Our findings suggest a role for Sp17 in tumor metastasis and aggressiveness. Whether Sp17 can be used as a prognostic marker for breast cancer will require a study of a larger sample size.

Legal entity responsible for the study

The Ethics Committee of the Sichuan University.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

278P - Intratumoral heterogeneity on dedicated breast positron emission tomography before chemotherapy predicts the outcome of neoadjuvant chemotherapy in breast cancer

Presentation Number
278P
Lecture Time
12:45 - 12:45
Speakers
  • Norio Masumoto (Hiroshima, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Dedicated breast positron emission tomography (DbPET) can detect intratumoral heterogeneity using 18F-fluorodeoxyglucose (FDG). We have proved that intratumoral heterogeneous distribution of FDG on DbPET was significantly related with high nuclear grade and high Ki-67 proliferation index (Breast Cancer Res Treat 2018; 171:315–23). We aimed to evaluate whether intratumoral heterogeneous distribution of FDG on DbPET can predict the effects of neoadjuvant chemotherapy (NAC) on breast cancer.

Methods

We evaluated 58 consecutive patients with breast cancer who underwent DbPET before NAC concurrently between August 2016 and March 2018. The relationships between the pathological response for NAC and the maximum standard uptake values (SUVmax) of DbPET, including estrogen receptor (ER) and human epidermal growth factor receptor type-2 (HER2) statuses, and the intratumoral heterogeneous distribution of FDG on DbPET, were evaluated.

Results

Breast cancer with intratumoral heterogeneous distribution of FDG on DbPET showed a tendency to be related with pathological complete response (pCR) (Table). The SUVmax of DbPET showed an increasing tendency with intratumoral heterogeneous distribution. ER positive-breast cancer with intratumoral heterogeneous distribution showed a tendency to be related with pCR.

Relation between biological factors and pathological response

pCRNon-pCRp
Grade0.17
1–2310
32025
Ki-670.35
< 20%14
≥ 20%2231
ER0.07
positive1524
negative811
HER20.06
positive1311
negative1024
DbPET, intratumoral distribution0.23
Heterogeneity1924
Homogeneity411

Conclusions

The SUVmax of DbPET associates with intratumoral heterogeneous distribution. In addition, intratumoral heterogeneity on DbPET provides predictive value for achieving pCR on ER positive-breast cancer and might inform therapeutic decisions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

279P - Results from NRG Oncology/NSABP protocol DMP-1: Physician Counseling

Presentation Number
279P
Lecture Time
12:45 - 12:45
Speakers
  • Christine Holmberg (Berlin, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Although selective estrogen receptor modulators (SERMs) reduce the risk of developing breast cancer (BC) in women at increased risk of the disease, there are also risks to consider. Guidelines suggest that such women should be counseled on risk-reducing options including SERMs. However, overall uptake is low. Previous results of DMP-1 showed that the health care provider’s (HCP) recommendation plays an important role in a woman’s decision to use a SERM. In this secondary analysis we aimed to better understand the counseling process of HCPs in the clinical care setting.

Methods

Women (N = 1,023) and their HCP discussed SERM use for BC risk reduction and were asked about the counseling, including risks and benefits presented and whether the HCP recommended SERM use. HCPs were also asked to report on the reasons for their recommendation and if the patient was likely to take a SERM or not. We describe the counseling and evaluate the agreement between the HCPs’ and women’s responses.

Results

HCPs reported on 1,022 counseling sessions. Benefits of SERMs in BC risk reduction were discussed in 96% of consultations; the risk of thromboembolism, endometrial cancer, and menopausal symptoms was discussed in > 86%; the risk of cataracts and decrease in libido in < 58%. Five HCPs reported no SERM discussion and were excluded. 66% of HCPs based their recommendation of SERM use on the Gail model risk score. Data for 895 participants were available to evaluate agreement. There was a modest agreement between the women’s and the HCPs’ statements on SERM recommendation (kappa=0.50), with fair agreement on the strength of the recommendation (weighted kappa=0.22) and substantial agreement between a woman’s decision and the HCP’s assumption of what his/her patient would do (kappa=0.65).

Conclusions

Most severe medical risks associated with SERM use were discussed during the counseling. The fairly low percentage of discussions about potential sexual consequences was comparable to that of other studies. Overall, there was fair to moderate agreement between HCPs and women’s perceptions of the counseling. Of note, HCPs had a good sense of what treatment the counseled women would choose. Support: U10CA180868, -180822; UG1-CA189867.

Clinical trial identification

NRG Oncology/NSABP DMP-1; NCT01399359; Opened to accrual: 8-1-11.

Legal entity responsible for the study

NRG Oncology.

Funding

NRG Oncology via NIH Grants: U10CA180868, -180822; UG1-CA189867.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

280P - Neoadjuvant eribulin plus carboplatin vs. paclitaxel plus carboplatin in patients with triple-negative breast cancer (TNBC)

Presentation Number
280P
Lecture Time
12:45 - 12:45
Speakers
  • Larisa Gigolaeva (Saint Petersburg, RU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Eribulin is a novel microtubule poison, which has certain advantages as compared to taxanes in some laboratory experiments and shows clinical efficacy in breast cancer patients after failure of taxane and anthracycline treatment. Promising activity of neoadjuvant eribulin plus carboplatin combination was shown in previous TNBC studies [Kaklamani et al. Breast Cancer Res Treat, 2015]. This investigation aimed to directly compare the efficacy of neoadjuvant eribulin/carboplatin vs. paclitaxel/carboplatin doublets in TNBC patients.

Methods

61 TNBC patients (median age 45, range 31-76) were randomized to receive carboplatin AUC6 with either eribulin (1.1 mg/m2 on days 1 and 8, every three weeks) or paclitaxel (80 mg/m2 on days 1 and 8, every three weeks). Each patient was treated with four cycles of neoadjuvant therapy followed by surgery and four cycles of adjuvant FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2). After adjuvant chemotherapy, patients with breast-conserving surgery or with positive lymph nodes also received radiation treatment.

Results

The rates of clinical complete responses were similar in both cohorts (eribulin/carboplatin: 12/24 (50%); paclitaxel/carboplatin: 19/37 (51%)). Pathologic complete responses (pCR) were numerically less frequent in patients receiving eribulin [9/24 (38%) vs. 20/37 (54%)], although the difference was below statistical significance (p = 0.2). Five patients were carriers of deleterious BRCA1 alleles; pCRs were observed in 2/3 (67%) and 2/2 (100%) women in eribulin and paclitaxel arms, respectively. 56 patients had a follow-up above 12 months at the time of data analysis. 4/24 (17%) disease recurrences were documented in the eribulin arm, while only 1/32 (3%) TNBC relapse was noticed for paclitaxel (p = 0.15).

Conclusions

Eribulin plus carboplatin combination does not outperform, in terms of pathomorphological response to treatment, paclitaxel plus carboplatin doublet while given as a neoadjuvant treatment for triple-negative breast cancer.

Legal entity responsible for the study

Petrov's National Medical Research Center for Oncology.

Funding

Russian Science Foundation [grant number 14-25-00111].

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

Breast cancer, metastatic

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

281TiP - A phase Ib/II study of Durvalumab combined with dose-dense EC in neoadjuvant setting for patients with locally advanced luminal B HER2(-) or triple negative breast cancers (B-IMMUNE).

Presentation Number
281TiP
Lecture Time
12:45 - 12:45
Speakers
  • Alix Devaux (Brussels, BE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Most patients with advanced breast cancer (BC) do not respond to immunotherapy with immunostimulating antibodies. Breast tumours are considered poorly antigenic due to a low mutational load, yet they contain tumour-infiltrating lymphocytes (TILs). As continuous immune pressure selects tumours that escape immune destruction, there is growing interest for the use of immunostimulatory antibodies for early-stage cancers. Based on data suggesting that anthracyclines increase tumour immunogenicity, we initiated a phase Ib/II trial to study the safety and efficacy of the anti-PD-L1 antibody durvalumab combined to epirubicin in the neoadjuvant setting for localized BC.

Trial design

B-IMMUNE study is a multicentric prospective trial including luminal B HER2(-) and triple negative BC (TNBC) patients. The study includes two parts. First a phase Ib with a 3 + 3 design whose primary objective is to evaluate the safety of an increasing number of durvalumab infusions associated to dose-dense Epirubicin-Cyclophosphamide (EC) after weekly paclitaxel for 12 weeks in the neoadjuvant setting. Then, if the durvalumab-EC combination is safe, a phase II will be initiated with an open-label 4:1 randomization in favour of the experimental durvalumab arm. Its primary objective is to evaluate clinical efficacy based on the complete pathological response rate (pCR) compared to historical controls (15% for luminal B HER2(-) BC and 30% for TNBC). The phase II will include 24 luminal B HER2(-) BC patients and 22 TNBC patients, allowing to detect pCR rate improvements of 40% and 60%, respectively (α ≤ 0.1 and β ≤ 0.1). Exploratory objectives include the identification of predictive biomarkers for anti-PD-L1 efficacy with a focus on the TCR repertoires of tumour-infiltrating T cells collected before and after durvalumab. Translational research will evaluate the presence of tumour-specific CD8 T cells among TILs and the influence of durvalumab on this population using the control arm as a reference.

Clinical trial identification

NTC03356860, ONCOGHdC2015_01, November 29, 2017.

Legal entity responsible for the study

Grand Hôpital de Charleroi (GHdC).

Funding

AstraZeneca, Télévie (FNRS).

Disclosure

J. Carrasco: Research grant: AstraZeneca. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

282TiP - Real-world effectiveness of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: the RIBANNA study

Presentation Number
282TiP
Lecture Time
12:45 - 12:45
Speakers
  • Peter A. Fasching (Erlangen, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

In the double blind, placebo-controlled phase III MONALEESA-2 trial, the selective CDK4/6 inhibitor ribociclib in combination with letrozole significantly prolonged progression free survival (PFS) in patients who were treatment-naïve for HR+/HER2- advanced breast cancer (aBC). In 2017, Ribociclib was approved in combination with an aromatase inhibitor (AI) for the treatment of HR+/HER2- aBC (locally advanced or metastatic). However, real-world evidence for the effectiveness, safety and tolerability of ribociclib+AI in routine clinical practice is needed to further support its use.

Trial design

RIBANNA is a non-interventional study (NIS) running in Germany since Oct 2017. Up to 400 German sites are expected to enroll 3020 postmenopausal patients receiving ribociclib+AI, or endocrine monotherapy, or chemotherapy as first-line treatment for HR+/HER2- aBC. Data will be collected from clinical practice on the effectiveness, safety, tolerability, and duration of therapy, including impact on quality of life (QoL) in all three cohorts prescribed in line with the respective German prescribing guidelines. These data and the corresponding outcomes will be described for the three different cohorts. Further lines of treatment will also be documented in RIBANNA to gain insight into the outcome of sequential therapy. For this purpose, patients will be documented for up to 7 years in total. In addition, RIBANNA will collect information on QoL using validated patient reported outcome measures to assess the impact of routine ribociclib+AI treatment, endocrine monotherapy or chemotherapy. The RIBANNA study will provide the first real-world evidence regarding the treatment of HR+/HER2- aBC/mBC with the novel CDK4/6 inhibitor ribociclib, including insights into treatment regimen, sequence of therapies and impact on QoL.

Clinical trial identification

CLEE011ADE03.

Legal entity responsible for the study

Novartis Pharma GmbH.

Funding

Novartis Phrama GmbH.

Editorial Acknowledgement

Editorial assistance was provided by Product Lifecycle Services.

Disclosure

P.A. Fasching: Consulting: Amgen, Roche, Novartis, Pfizer, Roche, Celgene; Fees: Amgen, Roche, Novartis, Pfizer, Roche, Celgene; Research funding: Novartis, Pfizer, Celgene. T. Decker: Consulting: Novartis; Support for travel fees: Novartis. J. Heim: Employee: Novartis Pharma GmbH. C. Jackisch: Employee: Sana Klinikum Offenbach; Consulting: Roche Pharma AG, Genomic Health; Research funding: Novartis Pharma, Roche, AstraZeneca, Genomic Health. H-J. Lueck: Consulting: Roche, Tesaro, Novartis, Astrazeneca, Lilly, Pfizer; Fees: Pfizer, Astrazeneca, Tesaro, Novartis, Roche. D. Lüftner: Consulting: Novartis, Pfizer, Eli Lilly, Celgene, Loreal, AstraZeneca; Fees: Novartis, Pfizer, Eli Lilly, Celgene, Loreal, AstraZeneca. F. Marmé: Consulting: Novartis, Pfizer, AstraZeneca, Roche, Amgen, Celgene; Fees: Novartis, Pfizer, AstraZeneca, Roche, Amgen, Genomic Health, PharmaMar, Celgene, MSD. T. Reimer: Consultant: Department of Obstetrics and Gynecology, University of Rostock, Germany; Fees: Roche, Novartis, Amgen, Pfizer, AstraZeneca. A. Woeckel: Clinic Director; Fees: GSK, Pfizer, Novartis, Amgen, Jannsen-Cilag, Celgene, Hexal, Roche; Research funding: Roche.

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295P - Exploratory biomarker analysis in patients treated with vinorelbine plus everolimus or vinorelbine monotherapy as second-line treatment for HER2-negative advanced breast cancer. Final results from the randomized phase II trial VicTORia.

Presentation Number
295P
Lecture Time
12:45 - 12:45
Speakers
  • Thomas Decker (Ravensburg, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The purpose of the VicTORia trial was to evaluate efficacy and safety of the combined treatment of everolimus (EVE) and vinorelbine (VIN) compared to VIN monotherapy as second-line treatment for HER2-negative advanced breast cancer. The study was accompanied by an exploratory analysis of phosphoinositide 3 kinase subunit (PIK3CA) as potential predicitve marker for response.

Methods

Patients were randomized 1:1 to receive i.v. VIN at a dose of 25 mg/m2 on days 1, 8 and 15 q3w plus 5 mg EVE once daily or i.v. VIN at a dose of 25 mg/m2 on days 1, 8 and 15 q3w. The primary objective was progression-free survival (PFS). Safety and tolerability, overall survival (OS) and overall response rates were secondary objectives. The mutational status of PIK3CA was determined at baseline from plasma samples.The study was initially planned to enroll 166 patients.

Results

Between December 2011 and February 2016 138 patients were enrolled from 32 sites across Germany. Of 69 patients randomized to receive VIN plus EVE, 68 received treatment and 65 of 69 patients randomized to VIN monotherapy received treatment. Baseline characteristics were balanced. Median age was 63 and 62 years, ECOG 0-1 98.5% and 90.7%, postmenopausal status 79.4% and 80.0%, and visceral metastases 89.7% and 87.7%, respectively. Median PFS was 4.01 months [95% CI, 2.40-6.09] for the combination vs. 4.08 months [95% CI, 2.80-5.33] for VIN monotherapy (HR = 1.05 [0.730-1.512], log rank p = 0.7908). The median OS was not statistically different between treatment arms (VIN+EVE: 16.25 months [95% CI, 11.38-18.95] vs. VIN: 13.78 months [95% CI, 10.23-19.05]), log rank p = 0.9361). PIK3CA mutational status was neither associated with PFS nor with OS in the total patient cohort, in patients treated with VIN+EVE and in patients treated with VIN monotherapy, respectively.

Conclusions

The addition of EVE to VIN was not associated with a benefit in PFS. Overall survival also did not significantly differ between treatment arms. No correlation between PIK3CA mutation status and outcome was detected.

Clinical trial identification

EudraCT: 2011-001024-38.

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

Novartis.

Disclosure

T. Decker: Advisory role or expert testimony: Novartis; Advisory boards, other financial relationships, travel expenses: Novartis. N. Marschner: Advisory role or expert testimony: Novartis; Advisory boards, honoraria: Novartis; Other financial relationships, travel expenses: Novartis. A. Welt: Advisory role or expert testimony: Novartis; Advisory boards, financing of scientific research: Novartis. J. Rauh: Other financial relationships: Honoraria for documentation in clinical studies: Novartis. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

296P - Applicability of the Lung Immune Prognostic Index (LIPI) to metastatic Triple negative Breast Cancer (mTNBC) patients treated with Immune Checkpoint Targeted Monoclonal Antibodies (ICT mAbs)

Presentation Number
296P
Lecture Time
12:45 - 12:45
Speakers
  • Aurore Vozy (Paris, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Tumor-infiltrating lymphocytes are prognostic and predictive in TNBC. However, the level of activity of Immune Checkpoint Targeted Monoclonal Antibodies (ICT mAbs) remains low in this indication and biomarkers are needed to select for patients who could benefit from these treatments. Pretreatment LIPI, based on derived NLR (dNLR = neutrophils/[leucocytes-neutrophils]) and lactate dehydrogenase (LDH) assessment has been associated with outcomes for ICT mAbs in advanced NSCLC patients. We tested whether LIPI has the same impact on mTNBC patients’ outcome.

Methods

Biological and clinical data were retrospectively collected from mTNBC patients treated with ICT mAbs between Jan 2014 & Apr 2018 in our Drug Development Department. Three LIPI risk groups were studied: good (dNLR<3 & LDH<upper limit of normal (ULN)), intermediate (dNLR>3 or LDH>ULN), poor (dNLR>3 & LDH>ULN). The primary endpoint was progression-free survival (PFS) and the secondary endpoint was overall survival (OS).

Results

Forty-two patients were included with a median age of 45, 48% were ECOG 0 and the median prior chemotherapy lines was 3. Twenty-one percent of patients received a PD1/PD-L1 inhibitor as monotherapy, 79% had ICT mAbs combination. The median PFS and OS under ICT mAbs was 1.35 months (IC 95% 1.27; 2.93) and 13.5 months (5.9; not reached) respectively according to RECIST v1.1. LIPI classified 18 patients as good (43%), 18 patients (43%) as intermediate and 6 patients (14%) as poor risk group. Median PFS was 2.65, 1.32 and 0.85 months for good (GP), intermediate (IP) and poor prognosis (PP) respectively (P = 0.002). Median OS was 18.10 months for GP, 9.8 months for IP and 1.6 months PP (P = <0.0001). Metastatic cutaneous lesions were also associated with poor PFS with ICT mAbs in our cohort, HR 3.189, P = 0.0028. The PDL1 status does not seem to influence LIPI risk groups.

Conclusions

Applying baseline LIPI in mTNBC patients is feasible and is correlated with ICT mAbs outcomes for this population. A larger retrospective validation cohort is being evaluated and more data will be available for the ESMO presentation.

Legal entity responsible for the study

Varga Andréa.

Funding

Has not received any funding.

Disclosure

J-C. Soria: Full time employee: MedImmune AstraZeneca since September 2017. C. Massard: Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Orion. B. Besse: AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Servier, Onxeo, OncoMed, Inivata, OSE Pharma, Loxo. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

297P - Peripheral Blood Mononuclear Cell Biomarkers Predict Response to Immune Checkpoint Inhibitor Therapy in Metastatic Breast Cancer

Presentation Number
297P
Lecture Time
12:45 - 12:45
Speakers
  • Yuan Yuan (Duarte, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The role of immune checkpoint PD-1/PD-L1 inhibitor (ICI) in breast cancer (BC) is being investigated in clinical trials. Preclinical evidence strongly supports the synergistic effects of CDK4/6 inhibitor and ICI. A phase II trial is testing the safety and efficacy of the combination of letrozole, palbociclib and pembrolizumab in patients with hormone receptor positive (HR+) BC (NCT02778685). Currently, there is no well-defined circulating biomarker to predict response to ICI.

Methods

Peripheral blood mononuclear cells (PBMC) were collected at day 1 of cycles 1 (pre-treatment), 2, 4, 6 and 8. The comprehensive characterization of 14 innate cell types, 7 adaptive T-cells, and 16 exhaustion-related T-cells was performed using 15-color flow cytometry. Core biopsies were taken at baseline and optionally on-study to assess immune cell subsets.

Results

Preliminary analysis included nine patients with the following responses by RECIST 1.1: 1 complete response, 4 partial responses, 2 stable disease, and 2 progression of disease. Analysis showed correlation of clinical response to high baseline levels of γδ T-cells (r = 0.74, p = 0.02) and exhausted T-cells: CD4+PD-1+KLRG1+ (r = 0.74, p = 0.02), CD4+PD-1+CD160+ (r = 0.71, p = 0.02), and CD4+PD-1+TIM3+ (r = 0.71, p = 0.03). Most patients showed a decrease in the number of CD33hi myeloid-derived suppressor cells (p = 0.04) and CD4+PD-1+TIGIT+ exhausted T-cells (p = 0.04) in peripheral blood at C2D1. Strong indicators of clinical response included increased CD33low myeloid-derived suppressor cells (r = 0.70, p = 0.04) and decreased type-1 CD8+ T-cells (r = 0.81, p = 0.009) at C4D1.

Conclusions

High pre-treatment peripheral blood exhausted CD4+ T-cells is associated with clinical response to ICI in HR+BC. Further analysis including tumor tissue immune profiling is currently ongoing to verify these findings.

Clinical trial identification

NCT02778685.

Legal entity responsible for the study

City of Hope.

Funding

City of Hope, Merck, Pfizer.

Disclosure

Y. Yuan: Industry funded research: Pfizer, Merck, Puma, GTX, Novartis, Eisai; Advisory board: Puma, Novartis, Eisai; Speaker Bureau: Eisai. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

298P - Circulating exosomal microRNA profiling to depict mechanisms of chemotherapy resistance among triple negative breast cancer

Presentation Number
298P
Lecture Time
12:45 - 12:45
Speakers
  • Yunjie He (Nanjing, CN)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Chemotherapeutic resistance leads to high mortality among triple negative breast cancer (TNBC) patients and underlying mechanisms are poorly understood. Exosomes have become new area of interest for liquid biopsy. MicroRNAs (miRNAs), as the most important inclusions in exosomes, are ideal candidate biomarkers and therapeutic targets.

Methods

We isolated exosomes and analyzed exosome-carried miRNA signatures in several TNBC cells lines sensitive or resistant to adariamycin, docetaxel or cisplatin. The resistance transfer capacity was determined by flow cytometry after sensitive cells incubated 48 hours with exosomes from drug-resistant cells. Locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH) was performed to detect exosomal miRNA molecule transfer. Animal mode was constructed to evaluate treatment feasibility using miRNA-modified exosomes. Serum exosomes from 40 TNBC stage IV patients who underwent chemotherapy before or after progressive disease (PD) status were isolated to analyze miRNA profiling for potential biomarker identification.

Results

We successfully isolated and identified exosomes from several drugsensitive and resistant TNBC cell lines and patients. Exosomal miR-222, miR-4443, miR-100, miR-17, miR-210 were found significantly upregulated from chemotherapy-resistant cells. Incubation of exosomes from the resistant cells with the sensitive cells resulted in increasing resistant capacity among sensitive cells. Exosomal miRNA molecule transfer was detected using LNA-ELF-FISH. Transfection of synthesized miRNAs competitors into exosomes increased drug sensitivity in vivo. Exosomal miR-222, miR-4443, miR-100, miR-17, miR-210 were also found upregulated significantly from serums of patients after PD status. These five miRNAs were able to differentiate patients with PD status from those with CR or PR status with at least 89% accuracy.

Conclusions

Exosomes from chemotherapy-resistant TNBC cells could transfer drug resistance to sensitive cells via exosomal miRNAs. A circulating exosomal microRNA profiling was estabilished for potential biomarkers and therapeutic target identification.

Legal entity responsible for the study

Jinhai Tang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

299P - The Prevalence of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer (BELLE2, BELLE3 and BOLERO2 clinical trials)

Presentation Number
299P
Lecture Time
12:45 - 12:45
Speakers
  • Kitty Wan (Basel, CH)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Breast cancer (BC) is the most common form of malignant tumor in women worldwide. 60-70% of BC are hormone receptor-positive (HR+), HER2-negative (HER2–). The purpose of this analysis was to enhance understanding on the epidemiology for women with PIK3CA-mutant HR+/HER2– metastatic breast cancer (mBC).

Methods

PIK3CA mutations were tested from tumor biopsy (N = 1617) and circulating tumor DNA (ctDNA) (N = 1466) from patients enrolled into BOLERO-2, BELLE-2 and BELLE-3, which are three randomized Phase III studies in HR+/HER2– mBC. Various PIK3CA mutation testing methods were applied, including Next-Generation Sequencing (NGS) and Polymerase Chain Reaction (PCR) for tumor biopsies, as well as BEAMing and droplet digital PCR for ctDNA samples.

Results

Prevalence of the PIK3CA mutations among tissue biopsies ranged from 34.1% to 41.1% while prevalence of the PIK3CA mutations among liquid biopsies ranged from 27.5% to 43.3%. Besides gene-level analysis, the PIK3CA prevalence by hot spots and by exons was examined as well. Further, subgroup analysis of PIK3CA prevalence had been conducted based on patient cohort (2L vs 3L), mutation testing methods, ethnicity, biopsy source (primary tissue vs metastatic) and previous treatment.

Conclusions

PIK3CA mutations (specifically hotspots H1047R, E545K and E542K) frequently occur in HR+/HER2– mBC. The prevalence of PIK3CA mutations are in a relatively narrow range across the three randomized Phase III studies in HR+/HER2– mBC regardless of tissue types and testing methods.

Legal entity responsible for the study

Novartis Pharma.

Funding

Novartis Pharma.

Disclosure

K. Wan: Employment: Novartis Pharma AG; Stock options: Novartis. Y.A. Wang, N. Babbar, M. Kaper, M. Fritzemeier: Employment: Novartis Pharmaceutical Corporation; Stock options: Novartis.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

300P - Differential molecular signature in patients from African origin with Triple-Negative Breast Cancer

Presentation Number
300P
Lecture Time
12:45 - 12:45
Speakers
  • Ana T. Matias (Lisbon, PT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Breast cancer (BC) is more aggressive in pre-menopausal women of Black race (BW). These women usually have worse prognosis and higher mortality rate when compared with patients of other races, even when socioeconomic factors are accounted for. Triple-negative BC (TNBC), the most aggressive and less treatable BC, due to the lack of therapeutic targets, such as oestrogen and progesterone receptor or HER2, is more frequently diagnosed in these young BW.

Methods

To identify the driving biological factors of this racial disparity we performed a comprehensive differential gene expression (DGE) analysis using the R package edgeR and RNA-sequencing BC data from The Cancer Genome Atlas, which has specifically USA data. In a total of 1097 BC patients, 183 are BW, 32 with TNBC (17.5% of all BW); 757 are White, 69 with TNBC (9.1%); and 61 are Asian, 8 with TNBC (13.1%).

Results

DGE between BW with TNBC and TNBC patients of other races revealed 251 up- and 269 downregulated genes (adjusted p-value ≤ 0.05, |log2(Fold Change)| ≥ 1, applied in all the analysis). To remove genes associated with race alone and not with TNBC in BW per se, we performed a DGE analysis between all non-TNBC cases in BW and all non-TNBCs in the other races, resulting in 315 up- and 139 downregulated genes in non-TNBCs of BW. Common genes between the two analyses were identified and extracted from the first list, resulting in 198 up- and 250 downregulated genes exclusively differentially expressed in TNBC of BW. Our candidates include genes related to insulin-resistance and obesity (e.g. FBXO2 [p-adj = 2.07E-04, log2FC = 1.58], POU2AF1 [p-adj = 1.80E-03, log2FC = 1.43]), and epithelial-mesenchymal transition and metastasis (e.g. FOXF2 [p-adj = 9.51E-05, log2FC = 1.39], NOTCH3 [p-adj = 9.51E-05, log2FC = 1.35]). These genes are being validated using formalin-fixed paraffin-embedded TNBC tissues from BW, collected from different Portuguese hospitals and from a Mozambican hospital, where tumour tissue is compared to normal adjacent tissue by qRT-PCR, immunohistochemistry and Western blot.

Conclusions

Our work will unveil the molecular signature(s) that characterise and define molecularly TNBC in BW and, ultimately, will guide the development of new therapeutics for this unmet medical problem.

Legal entity responsible for the study

CEDOC, Nova Medical School, Lisbon, Portugal.

Funding

Fundação para a Ciência e Tecnologia (PD/BD/114053/2015); iNOVA4Health (UID/Multi/04462/2013 – LISBOA-01-0145-FEDER-007344).

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

301P - Analysis of the JAK2 gene in TNBC

Presentation Number
301P
Lecture Time
12:45 - 12:45
Speakers
  • Libor Stanek (Prague, CZ)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The JAK2 gene is located on chromosome 9p24.1, its product is a tyrosine kinase protein that plays a role in signal transduction between membrane receptors for growth factors and intracellular signaling molecules and is also involved in cytokine signaling. Mutation V617F of JAK2 (Janus kinase 2) causes violation of autoinhibiting activity and promotes malignant transformation and proliferation. Recent studies, however, indicate a possible amplification of somatic chromosome 9p24.1 region encoding the JAK2 in triple-negative breast cancer (TNBC) in connection with a poorer prognosis and shorter survival.

Methods

The aim of our pilot study was to perform a cytogenetic and molecular biological analysis of the JAK2 gene in a cohort of 40 patients diagnosed and confirmed with TNBC. The FISH method was used to analyze numerical changes and translocations, including the detection of possible merger partners. In the next step mutation analysis was by PCR and direct sequencing performed.

Results

On the basis of cytogenetic and molecular changes of the JAK2 gene, it can be stated that the numerical, structural and molecular changes occur in TNBC at a high frequency. In addition to amplification which is a potential predictor of ruxolotinib inhibition, a number of numerical and structural changes (including point mutations) of the gene was detected (amplification detected in 25% of cases, polysomy detected in 15% of cases, monosomy detected in 5% of cases, break detection in 10% of cases, amplification/break detected in 10% of cases). Mutational analysis showed the presence of the V617F mutation in 15% of cases where there was normal cytogenetics.

Conclusions

These changes may potentially cause worse response to treatment with an inhibitor and will require us to focus attention in this direction.

Legal entity responsible for the study

First Faculty of Medicine.

Funding

This work was supported by the Charles University research program PROGRESQ 28 (Oncology).

Editorial Acknowledgement

This work was supported by the Charles University research program PROGRES Q 28 (Oncology)

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

302P - A risk score integrating lymphocytes ratios (LRs) and lactate dehydrogenase (LDH) levels to predict prognosis in metastatic breast cancer (MBC) patients.

Presentation Number
302P
Lecture Time
12:45 - 12:45
Speakers
  • Giacomo Pelizzari (Udine, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and LDH levels have been associated with worse prognosis in several malignancies, including MBC. This study aimed at exploring the prognostic impact of a novel risk score, integrating baseline LRs and LDH levels in MBC patients (pts).

Methods

This retrospective study analyzed 396 consecutive pts with a diagnosis of MBC, treated between 2007 and 2017 at the Oncology Department of Udine (Italy). MLR and NLR cut-offs were previously obtained through ROC analysis using propensity score-matched healthy controls (Gerratana et al 2018). The LDH cut-off value (480 U/L) was chosen according to the local laboratory upper reference limit. Based on these data, an integrated LRs-LDH score (LLS) was calculated ranging from 0 (LRs and LDH low), through 1 (LRs or LDH high), to 2 (both LRs and LDH high). The prognostic impact of baseline LLS was investigated through Cox regression, and differences in survival were tested by log-rank test.

Results

After a median follow-up of 52.8 months, median overall survival (OS) was 30.9 months and median progression free survival (PFS) was 9.2 months. Pts with baseline elevated MLR, NLR or LDH were 64.2% (251/391), 70.8% (277/391), and 31.5% (70/222), respectively. The 78.8% (308/391) of pts had elevated LRs (MLR, NLR or both). Considering subgroup analysis, no interaction was seen between LDH and LRs. By multivariate analysis, after adjustment for molecular profiles, performance status, number of metastatic sites, central nervous system and liver involvement, a worse prognosis in terms of OS was seen for pts with elevated levels of both LRs and LDH (LLS 2: HR 2.41, 95% CI: 1.31-4.37, p=.003), compared to pts with normal LRs and LDH (LLS 0). Notably, significant differences in OS were observed according to the LLS (LLS 2: median OS 19.2 months, LLS 1: median OS 43.9 months, LLS 0: median OS 54.9 months; p<.0001).

Conclusions

Baseline LLS is able to predict survival in pts with MBC and provides independent prognostic information. Prospective studies are needed to validate this novel score and to explore how it may affect different treatment strategies.

Legal entity responsible for the study

University of Udine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

303P - EMBRACA: Comparison of efficacy and safety of talazoparib (TALA) and physician's choice of therapy (PCT) in patients (pts) with advanced breast cancer (aBC), a germline BRCA1/2 mutation (gBRCAm), and prior platinum treatment

Presentation Number
303P
Lecture Time
12:45 - 12:45
Speakers
  • Miguel Martín (Madrid, ES)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

TALA is a dual-mechanism PARP inhibitor that prevents DNA damage repair by trapping PARP on DNA, resulting in cell death in BRCA1/2-mutated cells.

Methods

EMBRACA is an open-label, randomised, 2-arm phase 3 trial in which efficacy and safety of TALA (1 mg/day) is compared with standard single-agent PCT (capecitabine, eribulin, gemcitabine, or vinorelbine) in pts with aBC and gBRCAm. In this analysis clinical outcomes were assessed in 2 subgroups of pts who had either received prior platinum (PP) or had no prior platinum (NPP) treatment.

Results

Of 431 pts randomised, 76 had PP in any setting (46 TALA; 30 PCT) and 355 were NPP (241 TALA; 114 PCT). Mean (SD) age was 46.4 (11.15) years. Pts in all groups had received a median of 1 prior cytotoxic regimen for aBC. TALA demonstrated a statistically significant improvement in both objective response rate (odds ratio [OR] [95% CI]: PP 3.16 [0.88-15.67], P=.0456; NPP 5.36 [2.89-9.89], P<.0001) and progression-free survival (hazard ratio [95% CI]: PP 0.76 [0.40-1.45], P=.41; NPP 0.52 [0.39-0.71], P<.0001) compared with PCT. Mean (SD) duration of TALA therapy was 7.2 (6.52) mo (PP) and 8.7 (7.09) mo (NPP), with 15% (PP) and 19% (NPP) of pts receiving TALA for ≥12 mo. Median duration of response (DOR) to TALA was longest in NPP pts (5.4 mo), followed by PP pts (4.2 mo); pts receiving PCT had a DOR of approximately 3.0 mo regardless of prior platinum status. Pts on TALA achieved a clinical benefit rate at 24 weeks (PP 59%; NPP 71%) with OR significantly favouring TALA over PCT in both groups. Of pts receiving TALA, nausea was the most common adverse event (AE) in PP pts (59%) and anaemia in NPP pts (53%). Serious AEs occurred in both PP (33%) and NPP pts (32%) taking TALA.

Conclusions

In pts with advanced gBRCAm breast cancer, TALA demonstrated statistically significant improvements in clinical outcomes for both PP and NPP subgroups compared with PCT. Although TALA treatment benefitted both groups, the benefit was greater if TALA was used before platinum therapy.

Clinical trial identification

NCT01945775.

Legal entity responsible for the study

Pfizer, Inc.

Funding

This study was sponsored by Medivation LLC, a Pfizer company.

Editorial Acknowledgement

Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.

Disclosure

M. Martín: Consulting fees: Pfizer; Fees for non-CME services received directly from commercial interests or their agents: Pfizer. H.S. Rugo: Fees for contracted research to the University of California: Eisai, Genentech, GSK, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Pfizer, Plexxikon; Travel: Lilly, Mylan, Puma. J. Ettl: Consulting fees: Novartis, Pfizer, Roche, Eisai; Contracted research: Celgene; Honoraria: Pfizer, Roche, Teva, and Pierre Fabre. S.A. Hurvitz: Contracted research: Amgen, Bayer, BioMarin, BI, Cascadian Therapeutics, Dignitana, Genentech/Roche, GSK, Lilly, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology, Sanofi; Travel: Bayer, Lilly, Novartis, and OBI Pharma. D. Markova, I.C. Tudor: Employee: Pfizer, Inc. J.L. Blum: Consulting fees: Pfizer. A.L. Hannah: Consulting fees: Basilea, Medivation/Pfizerand Nektar; Ownership interest: NeoGenomics Laboratories. J.K. Litton: Institutional-contracted research: Pfizer, Novartis, EMD-Serono, AstraZeneca, GlaxoSmithKline, Genentech; Advisory board participation: AstraZeneca and Pfizer, both uncompensated. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

304P - EMBRACA: Efficacy and safety in comparing talazoparib (TALA) with physician's choice of therapy (PCT) in patients (pts) with advanced breast cancer (aBC) and a germline BRCA mutation (gBRCAm); BRCA1/BRCA2 subgroup analysis

Presentation Number
304P
Lecture Time
12:45 - 12:45
Speakers
  • Anthony Gonçalves (Marseille, FR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

TALA is a dual-mechanism PARP inhibitor that traps PARP on DNA, prevents DNA damage repair, and causes cell death in BRCA1/2-mutated cells.

Methods

EMBRACA is an open-label, randomized, 2-arm phase 3 trial comparing the efficacy and safety of TALA (1 mg/day) with standard single-agent PCT (capecitabine, eribulin, gemcitabine, or vinorelbine) in pts with aBC and a gBRCAm). In this analysis clinical outcomes were assessed in BRCA1 and BRCA2 subgroups.

Results

Of 431 pts randomized, 196 were BRCA1 (133 TALA; 63 PCT), 235 were BRCA2 (154 TALA; 81 PCT). Mean (SD) age was 45.4 (11.66) years (BRCA1) and 50.4 (11.45) years (BRCA2). Pts in all groups had received a median of 1 prior cytotoxic regimen for aBC. TALA demonstrated a statistically significant improvement in both objective response rate (odds ratio [OR] [95% CI] BRCA1 7.01 [2.99-19.54]; BRCA2 4.15 [1.90-8.52]; both P<.0001) and progression-free survival (hazard ratio [95% CI] BRCA1 0.59 [0.39-0.90]; BRCA2 0.47 [0.32-0.70]) in BRCA1 and BRCA2 subgroups compared with PCT. Mean (SD) duration of TALA therapy was 7.5 (7.07) mo (BRCA1) and 9.2 (6.88) mo (BRCA2), with 15% (BRCA1) and 22% (BRCA2) of pts receiving TALA for ≥12 mo. Median duration of response (DOR) to TALA was longest in BRCA2 pts (6.3 mo), followed by BRCA1 pts (4.2 mo); BRCA1 and BRCA2 pts receiving PCT had a DOR of approximately 3.0 mo. Pts on TALA achieved a clinical benefit rate at 24 weeks (BRCA1 62%; BRCA2 74%) with OR significantly favouring TALA over PCT in both groups. Of pts receiving TALA, anaemia was the most common adverse event (AE) in BRCA1 pts (56%) and fatigue in BRCA2 pts (50%). Serious AEs occurred in both BRCA1 and BRCA2 pts (32%) receiving TALA.

Conclusions

In pts with advanced gBRCAm breast cancer, TALA demonstrated statistically significant improvements in clinical outcomes for both BRCA1 and BRCA2 subgroups compared with PCT.

Clinical trial identification

NCT01945775.

Legal entity responsible for the study

Pfizer, Inc.

Funding

his study was sponsored by Medivation LLC, a Pfizer company.

Editorial Acknowledgement

Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.

Disclosure

H.S. Rugo: Fees for contracted research to the University of California: Eisai, Genentech, GSK, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Pfizer, Plexxikon; Travel: Lilly, Mylan, Puma. J. Ettl: Consulting fees: Novartis, Pfizer, Roche, and Eisai; Contracted research: Celgene; Honoraria: Pfizer, Roche, Teva, Pierre Fabre. S.A. Hurvitz: Contracted research: Amgen, Bayer, BioMarin, BI, Cascadian Therapeutics, Dignitana, Genentech/Roche, GSK, Lilly, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology, Sanofi; Travel: Bayer, Lilly, Novartis, OBI Pharma. Martín: Consulting fees: Pfizer and fees for non-CME services received directly from commercial interests or their agents: Pfizer. M. Al-Adhami, I.C. Tudor: Employment: Pfizer, Inc. J.L. Blum: Consulting fees: Pfizer. A.L. Hannah: Consulting fees: Basilea, Medivation/Pfizer and Nektar; Ownership interest: NeoGenomics Laboratories. J.K. Litton: Institutional-contracted research: Pfizer, Novartis, EMD-Serono, AstraZeneca, GlaxoSmithKline, Genentech; Advisory board participation: AstraZeneca and Pfizer, both uncompensated. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

305P - Exposure-efficacy progression-free survival (PFS) analyses of breast cancer patients with germline BRCA1/2 mutations receiving talazoparib in the phase 3 EMBRACA trial

Presentation Number
305P
Lecture Time
12:45 - 12:45
Speakers
  • Yanke Yu (La Jolla, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Talazoparib is a potent, orally bioavailable, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that is currently under development for the treatment of a variety of cancers. This exposure-response (ER) analysis characterized the relationship between talazoparib exposure and PFS in patients with locally advanced and/or metastatic breast cancer with germline breast cancer susceptibility gene (BRCA) mutations based on the phase 3 EMBRACA trial.

Methods

285 patients, who were treated with talazoparib and had available pharmacokinetic (PK) parameters from the phase 3 EMBRACA trial, were included in the analysis. There were 185 PFS events at the data cut of the analysis. The apparent talazoparib clearance (CL/F) for each patient was obtained from a population PK analysis. To account for dose modifications over time, the ER analysis used a time-varying exposure metric (Cavg,t) for talazoparib exposure. At each PFS event, the talazoparib exposures up to the time of the PFS event t were calculated for all patients at risk using average daily dose intensity up to time t and CL/F and correlated with the probability of having a PFS event using the Cox proportional hazards model. Other potential prognostic factors were also tested as covariates for PFS. The significant covariates identified in univariate analyses were further examined for significance in multi-variate analyses.

Results

The ER analysis for PFS showed that there was a significant correlation between PFS and talazoparib exposure. A longer PFS was associated with higher talazoparib exposure. In addition, longer PFS was also associated with lower baseline lactate dehydrogenase. PFS was longer in patients without visceral disease than patients with visceral disease. A diseasefree interval of > 12 months was associated with a longer PFS than that of ≤ 12 months.

Conclusions

PFS was found to be associated with Cavg,t, and a longer PFS was associated with a higher talazoparib exposure. This supports using 1 mg QD, the maximum tolerated dose, as the recommended dose for talazoparib.

Clinical trial identification

NCT01945775.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Editorial Acknowledgement

Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.

Disclosure

J.K. Litton: Institutional-contracted research: Pfizer, Novartis, EMD-Serono, AstraZeneca, GlaxoSmithKline, Genentech; Advisory board participation: AstraZeneca and Pfizer, both uncompensated. Y. Yu, M. Elmeliegy, I.C. Tudor, A. Czibere, J. Zheng, D.D. Wang: Employment: Pfizer, Inc.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

306P - Exposure-safety analyses in breast cancer patients with germline BRCA1/2 mutations receiving talazoparib (TALA) in EMBRACA and ABRAZO trials

Presentation Number
306P
Lecture Time
12:45 - 12:45
Speakers
  • Mohamed Elmeliegy (East Hanover, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

TALA is a potent PARP inhibitor. Efficacy and safety profiles of once-daily TALA 1 mg were established in advanced breast cancer patients (pts) in the phase 3 EMBRACA and phase 2 ABRAZO trials. Approximately 60% of pts experience dose modification due to an adverse event (AE). This analysis characterized the relationship between TALA exposure and grade 3 or higher anemia, neutropenia, and thrombocytopenia, the most common AEs leading to dose modification.

Methods

Safety and pharmacokinetic (PK) data from 367 TALA-treated pts (285 EMBRACA, 82 ABRAZO) were included in a pooled analysis. To account for dose modifications over time, individual time-varying concentration from time 0 up to the time of each safety event (Cavg,t) was calculated at each event time using average daily dose intensity and apparent TALA clearance as obtained from population PK analysis. The relationship between Cavg,t, as well as other potential prognostic factors and the selected safety events was evaluated using Cox proportional hazard (PH) models. Significant covariates in univariate analyses were further examined in multi-variate analyses.

Results

Visual examination suggested a higher Cavg,t in pts with anemia and thrombocytopenia events vs pts without events. Cox PH models indicated that a higher risk of anemia and thrombocytopenia was associated with higher Cavg,t. For anemia, the HR (95% CI) for Cavg,t (ng/mL) was 1.3 (1.12, 1.4), P = 3.03. For thrombocytopenia, the HR (95% CI) for Cavg,t (ng/mL) was 1.2 (1.01, 1.3), P = 0.0394. A trend for association between higher Cavg,t and neutropenia was observed although the relationship was not statistically significant (P = 0.0633). Higher risk of all tested safety endpoints was associated with lower baseline hemoglobin. Higher risk of neutropenia was associated with lower absolute neutrophil count and lower body weight.

Conclusions

A higher risk of anemia and thrombocytopenia was associated with higher TALA exposure. This finding supports the proposed management of TALA-related AEs through dosing interruption and reduction.

Clinical trial identification

NCT01945775, NCT02034916.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Editorial Acknowledgement

Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.

Disclosure

J.K. Litton: Institutional-contracted research: Pfizer, Novartis, EMD-Serono, AstraZeneca, GlaxoSmithKline, and Genentech; Advisory board participation: AstraZeneca and Pfizer, both uncompensated. N.C. Turner: Advisory board, honoraria and research funding: Pfizer and BioMarin. M. Elmeliegy, A. Czibere, Y. Yu, G.G. Wilson, I.C. Tudor, J. Zheng, D.D. Wang: Employment: Pfizer, Inc.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

307P - An international systematic review (SR) of breast cancer (BC) BRCA mutation (BRCAm) prevalence

Presentation Number
307P
Lecture Time
12:45 - 12:45
Speakers
  • Nigel Armstrong (York, GB)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Carriers of BRCAm have an increased risk of developing BC. Considering the availability of BRCAm-targeted advanced breast cancer (aBC) drugs and evolving treatment guidelines, an SR was conducted to summarise the prevalence of BRCAm carriers in the overall BC population and stratified by clinical and demographic subgroups in different countries.

Methods

This SR adhered to the Cochrane method. Electronic databases (eg, Medline & Embase; n = 7) and grey literature sources were searched (Jan 2012 to Nov 2017). Studies reporting on BC BRCAm prevalence were included. BRCA1/2m prevalence (including germline) in BC (overall and aBC), clinical (TNBC, HR+/HER2- BC), and demographic subgroups (race/ethnicity) were summarised.

Results

17,872 records were retrieved; 70 studies were included. Regions/countries: Europe (n = 16), USA (n = 33), Canada (n = 2), Australia (n = 2), Japan (n = 1), South Korea (n = 11), Russia (n = 2), and Israel (n = 3). Only 29 studies explicitly reported BRCA germline status with prevalence ranging from 1.8% in an overall BC population (Sardinia) to 59.52% in a study of BC with family history (Spain). BRCAm prevalence varied widely in 16 overall BC population studies ranging from 2.7% (France) to 23.6% (Italy). Broader BRCAm prevalence ranges were observed in 5 aBC studies, varying from 2% in an overall BC population (France) to 53.8% in a study of Ashkenazi Jews (Israel). 42 reported BRCA1m and BRCA2m separately with no consistent distribution pattern between the 2. In the 24 TNBC studies, prevalence varied from 9.3% in an overall BC population (Australia) to 73.3% in a study of BC with a family history (Israel). BRCA1m prevalence was higher in TNBC studies that reported BRCA1m separately from BRCA2m (16 of 24 studies). In 3 studies of HR+/HER2- BC, BRCAm prevalence varied from 5% (USA) to 9.9% (South Korea). BRCAm prevalence ranged from 14.2% (USA) to 53.8% (Israel) in those of Ashkenazi Jewish ancestry.

Conclusions

Reported BRCAm prevalence in BC varies widely in clinical and demographic subgroups across countries; there are few studies on aBC and most lack germline BRCAm status specification. Further BC BRCAm epidemiologic studies are warranted to validate the prevalence of BRCAm with germline status.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Editorial Acknowledgement

Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.

Disclosure

N. Armstrong, S. Ryder, C. Forbes, A. Chalker, J. Ross, R. Quek: Employee: KSR Ltd. who was paid by Pfizer Inc. to carry out this work.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

308P - Genetic screening, counselling, and treatment of BRCA mutation (BRCAm) carriers: a systematic review (SR) of international breast cancer (BC) guidelines

Presentation Number
308P
Lecture Time
12:45 - 12:45
Speakers
  • Carol Forbes (York, GB)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Considering the availability of BRCAm-targeted therapeutic drugs in BC and an evolving clinical guidelines landscape, an SR of international guidelines on screening and management of BRCAm BC patients was carried out.

Methods

The current SR adhered to Cochrane’s guidance. Major electronic databases (eg, Medline & Embase; n = 7) and grey literature sources were searched (Jan 2007 to Dec 2017). Latest guideline reporting recommendations (and evidence grades) on genetic screening, counselling, and BC treatment of BRCAm carriers were summarised. Guidelines specific to germline (gBRCAm) (ie, hereditary) were captured where available.

Results

3775 records were retrieved and 33 guidelines from Europe (n = 17), USA (n = 11), Canada (n = 3), Australia (n = 1), and Japan (n = 1) were included. Genetic counselling was recommended at multiple points in the care pathway, though the format (eg, frequency, decision tools) was not always clearly defined. US guidelines emphasised BRCAm testing should occur after specialised genetic counselling; other European guidelines were less prescriptive. BRCA testing eligibility criteria differed with some guidelines being less restrictive; US NCCN BC guidelines specified that HER2- BC patients eligible for single-agent therapy should strongly consider gBRCAm testing, while also having separate more restrictive high-risk BRCA testing criteria. Similar restrictive criteria were observed in some European guidelines. Fast-track BRCAm testing was recommended in the Netherlands if treatment choice affects BC survival, but only as part of a clinical trial in the UK. Other guidelines suggest testing only if it affects therapy decisions. ESMO ABC3 guidelines recommended platinum therapy for advanced BRCAm BC; more recent ESO-ESMO BCY3 and US NCCN guidelines recommended newly approved gBRCAm-targeted PARP inhibitor therapy.

Conclusions

Differences exist between regions and within organizations for guidelines regarding genetic screening, counselling, and treatment of BRCAm BC patients. Harmonisation of guidelines could optimise the identification and management of BRCAm BC patients.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Editorial Acknowledgement

Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.

Disclosure

C. Forbes, D. Fayter, S. de Kock: Employee: KSR Ltd. who were paid by Pfizer Inc. to carry out this work. C. Clar, K. Reid: Freelance reviewer working on behalf of KSR Ltd. who were paid by KSR Ltd to carry out this work. R. Quek: Employee: Pfizer Inc.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

309P - Efficacy and toxicity of endocrine therapy + cyclin-dependent kinases 4/6 inhibitors (iCDK4/6) in metastatic breast cancer patients according to gBRCA status

Presentation Number
309P
Lecture Time
12:45 - 12:45
Speakers
  • Luisina I. Bruno (Buenos Aires, AR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Endocrine therapy (ET) and iCDK4/6 has demonstrated efficacy in terms of progression free survival (PFS), and clinical benefit as first and second line treatment in hormone receptor positive (HR+), Her2 negative, metastatic breast cancer (MBC). Cost and toxicity has limited its worldwide indication. No predictive biomarkers of response or toxicity have been validated. The aim of this analysis is to explore the utility of the gBRCA status as a predictive factor of efficacy and toxicity in HR+, Her2 negative, MBC treated with the combination of ET + iCDK4/6.

Methods

Prospective cohort study of patients under ET+ iCDK4/6 toxicity registry. Next Generation Sequencing (NGS) for gBRCA1 and 2 and genetic counseling was offered according to physician regular practice.

Results

92 patients were available for analysis, 24 had been studied for gBRCA. Still 3/24 (12%) have pending results, but 21% (5/24) were positive (2 gBRCA1+, and 3 gBRCA2+), and 67% (16/24) were negative (gBRCAneg). Median age of the global cohort was 46 years old (range 27-84), only 21% were stage IV at onset. The overall clinical benefit was 48%, significantly better for gBRCAneg 81% (13/16) versus 20% (1/5), p-value 0.011213. PFS was 46 weeks for the global cohort (CI95% 43.7-57.4 months), with tendency to better results among gBRCAneg 57 weeks (CI95% 42.2-80.5) versus 47 weeks (CI95% 21.2-72.7) for gBRCA+. The overall toxicity grade 3-4 was 24% (23/96) without differences according to gBRCA status (gBRCA+ 20% versus gBRCAneg 25%, p-value 0.818769).

Conclusions

We observed a significantly higher clinical benefit with a tendency to higher PFS in gBRCAneg HR+, Her2 negative MBC under ET + iCDK4/6 treatment and similar toxicity in both groups. This exploratory analysis suggests a potential role for gBRCA status as a biomarker of efficacy in this scenario. We believe that prospective, pre-stratified and adequately powered studies warrants further investigation and could help to design the proper sequence of treatments in light of the availability of up-coming target therapies such as PARP inhibitors.

Legal entity responsible for the study

Alexander Fleming Institute.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

310P - Clinical Outcomes, Treatment Patterns and Health Resource Utilization (HRU) Among Metastatic Breast Cancer (mBC) Patients (pts) with Germline BRCA Mutation (gBRCAm)

Presentation Number
310P
Lecture Time
12:45 - 12:45
Speakers
  • Ruben Quek (San Francisco, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

With evolving gBRCAm BC guideline landscape, we present latest gBRCA testing rates among mBC US pts with HR+/HER2- or triple negative BC (TNBC); including clinical outcomes, treatment patterns and HRU in gBRCAm pts.

Methods

The Flatiron Health database was used in a real world retrospective analysis of mBC pts with HR+/HER2- or TNBC, ≥18 yrs old, diagnosed between Jan 2011-Feb 2018. Rates of gBRCA testing were assessed. One- to 5-yr overall survival (OS) post mBC diagnosis for gBRCAm HR+/HER2- and TNBC pts were estimated. Cox proportional hazards model was used to estimate OS of TNBC vs HR+/HER2-. Outcomes between TNBC vs HR+/HER2- pts were compared while adjusting for imbalances. Antineoplastic treatment was summarized and HRU patterns were analyzed using t-tests.

Results

The study included 12,021 mBC pts (10,291 HR+/HER2-; 1730 TNBC). Results for gBRCA testing were available for 16.7% of pts overall; (HR+/HER2-: 15.4%, TNBC: 24.2%). The most common 1st line treatments for gBRCAm TNBC were capecitabine (19%) and carboplatin/gemcitabine (15%) and 1st line treatments for gBRCAm HR+/HER2- included letrozole (10%) and fulvestrant (7%). Pts counts, OS estimates and HRU for gBRCAm carriers are shown in the table; Cox regression results showed lower OS for gBRCAm TNBC pts vs gBRCAm HR+/HER2- mBC pts, Hazard Ratio (HR+/HER2- / TNBC) and 95% CI 0.59 (0.34, 1.01). Estimated median OS and 5-yr OS rates are (33.9 mths, 22.3 mths) and (28.9%, 26.4%) for gBRCAm HR+/HER2- and TNBC pts respectively. Number of HRU visits per-pts-per-year were significantly higher among TNBC pts.

Conclusions

gBRCA testing rates among mBC pts with HR+/HER2- or TNBC were low. Among mBC pts with gBRCAm, 5-yr OS rates were < 29% for both HR+/HER2- and TNBC; poor prognosis and HRU burden demonstrates a significant unmet need for more targeted, less HRU-intensive treatment options among these pts.

HR+/HER2-TNBC
Total Patients (N = 12,021) n (%)10,291 (85.6)1730 (14.4)
Patients with gBRCA test results (n = 2005) n (%)1587 (79.2)418 (20.8)
Patients with gBRCAm (n = 229) n (%)165 (72.1)64 (27.9)
gBRCAm patients with ≥ 1st Line antineoplastic treatment (n = 188) n (%)142 (75.5)46 (24.5)
YearOverall Survival Estimates (%)
193.469.5
258.646.3
345.826.4
430.726.4
528.926.4
Number of Health Resource Utilization Visits (per patient per year) mean (std dev) *p < 0.05
Treatment Visits*17.4 (14.4)40.8 (21.8)
Lab Visits*24.2 (10.1)40.3 (44.2)
Vital Visits*27.4 (14.3)49.9 (66.8)
ALL*35.2 (30.3)65.0 (84.7)

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Disclosure

R. Quek, J. Mardekian: Employee: Pfizer Inc.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

311P - Early Results from an Open-label Phase 1b/2 Study of Eribulin Mesylate (EM) + Pegvorhyaluronidase Alfa (PEGHP20) Combination for the Treatment of Patients (Pts) with HER2-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)

Presentation Number
311P
Lecture Time
12:45 - 12:45
Speakers
  • Merill Shum (Whittier, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

HA in the tumor microenvironment can inhibit the effectiveness of anticancer agents. The novel biologic PEGPH20 degrades pathological HA accumulation. EM is a microtubule inhibitor approved for the treatment of pts with MBC who previously received ≤2 lines of systemic anticancer therapy for metastatic disease. Preclinical data showed the PEGPH20+EM combination resulted in enhanced anti-tumor effectiveness in HAaccumulating, triple-negative breast cancer (TNBC) xenografts. The primary objective of this Phase 1b study (NCT02753595) was to determine safety, tolerability and RP2D of PEGPH20+EM in pts with HER2neg MBC previously treated with ≤2 lines of systemic anticancer therapy in the metastatic setting.

Methods

Overall, 14 enrolled pts were treated IV at 2 PEGPH20 dose levels (DL1=3 µg/kg or DL0=1.6 µg/kg on D1, D7) + EM 1.4 mg/m2 on D1, D8 of a 21day cycle. 5 pts were treated at DL1, with 2 DLTs observed (G3 muscle cramp, G3 knee/leg pain); 6 pts were enrolled in DL0 with no further DLTs. An additional 3 pts were enrolled at DL0 (RP2D).

Results

All 14 pts were evaluable for safety and efficacy. Median age was 53 years (33–78 years); 14% (2/14) of pts had TNBC. Median number of treatment cycles was 6.0. Drug-related TEAEs occurred in 86% of pts during PEGPH20+EM therapy. 79% of pts had G ≥ 3 TEAEs. There were 3 SAEs (1 in DL1 and 2 in DL0). As of April 2018, the individual safety profile was as expected for PEGPH20 and EM; no new significant safety signals identified. Key pt characteristics and BORs are shown below. Out of the 5 pts with confirmed PR, 3 had 1 prior and 2 had no prior systemic anticancer therapy in the metastatic setting.

CategoryPEGPH20 (3 µg/kg)/PEGPH20 (1.6µg/kg)/Total
EM (1.4 mg/m2)EM (1.4 mg/m2)
(n = 5)(n = 9)(N = 14)
Enrollment Strata – n (%)
TNBC0 (0)2 (22)2 (14)
ER and/or PRo-positive5 (100)7 (78)12 (86)
ECOG Status – n (%)
04 (80)4 (44)8 (57)
11 (20)5 (56)6 (43)
No. Prior Systemic Anticancer Therapy in Metastatic Setting – n (%)
01 (20)4 (44)5 (36)
13 (60)5 (56)8 (57)
21 (20)0 (0)1 (7)
Confirmed BOR – n (%)
CR0 (0)0 (0)0 (0)
PR2 (40)3 (33)5 (36)
SD1 (20)2 (22)3 (21)
PD1 (20)3 (33)4 (29)
Not evaluable/Unknown1 (20)1 (11)2 (14)
ORR (CR+PR) – n (%)2 (40)3 (33)5 (36)
DCR (CR+PR+SD) – n (%)3 (60)5 (56)8 (57)

Abbreviations: BOR=best overall response; CR=complete response; DCR=disease control rate; ECOG=Eastern Cooperative Oncology Group; EM=eribulin mesylate; ER=estrogen receptor; MBC=metastatic breast cancer; ORR=objective response rate; PD=progressive disease; PEGPH20=pegvorhyaluronidase alfa; PR=partial response; PRo=progesterone receptor; SD=stable disease; TNBC=triple-negative breast cancer

Conclusions

These early results are encouraging with a 36% ORR and 57% DCR, suggesting that PEGPH20 + anti-breast cancer agents such as EM warrant further investigation in pts with HER-2 neg MBC. A complete dataset is expected in October 2018.

Clinical trial identification

NCT02753595.

Legal entity responsible for the study

Eisai, Inc.

Funding

Eisai, Inc. in collaboration with Halozyme Therapeutics, Inc.

Editorial Acknowledgement

Editorial assistance provided by Paragon, Knutsford, UK.

Disclosure

C. Savulsky, W. Zhu, P. Iyer, D. Xing: Employee: Eisai C. Berman, N.A. Lokker: Employee: Halozyme Therapeutics. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

312P - Phase II clinical trial of first-line eribulin plus trastuzumab for advanced or recurrent HER2-positive breast cancer

Presentation Number
312P
Lecture Time
12:45 - 12:45
Speakers
  • Koichi Sakaguchi (Kyoto, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Eribulin mesylate has been approved for advanced or metastatic breast cancers subjected to at least two previous chemotherapy regimens. The present multicenter, phase II, single-arm study assessed the efficacy and safety of a first-line regimen of eribulin plus trastuzumab for untreated advanced or metastatic HER2-positive breast cancer.

Methods

Enrolled patients received eribulin (1.4 mg/m2 intravenously; I.V.) on days 1 and 8 of each 21-day cycle, an initial trastuzumab dose (8 mg/kg I.V.) on day 1, and 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. The primary endpoint was the RR. The secondary endpoints were PFS, OS, DOR, and safety. Twenty-eight patients (median age: 62.5 years) received a median of 12 (range: 2–53) cycles of eribulin plus trastuzumab.

Results

The RR was 53.6% (CR, 4; PR, 11) with a median PFS of 344 days. The clinical benefit rate was 64.0%. Grade 3/4 adverse events were observed in 12 (42.9%) patients. For details, neutropenia in 8 (28.6%) patients, peripheral neuropathy in 2 (7.1%) patient, interstitial pneumonia in 1 (3.6%) patient, ALT elevation in 1 (3.6%) patient, osteonecrosis of the jaw in 1 (3.6%) patient, and fatigue in 1 (3.6%) patient. The patient with osteonecrosis received denosumab, too. No symptomatic congestive heart failure was observed.

Conclusions

Combination therapy of eribulin plus trastuzumab is acceptable in efficacy and safety, and a capable option for first-line advanced or recurrent HER2-positive breast cancer.

Clinical trial identification

UMIN000009890.

Legal entity responsible for the study

Translational Reseach Informatics Center, Kobe, Japan.

Funding

Has not received any funding.

Editorial Acknowledgement

Editage edited English language.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

313P - Eribulin in metastatic breast cancer the UK experience,- a multi-centre retrospective 577 patient study

Presentation Number
313P
Lecture Time
12:45 - 12:45
Speakers
  • Mariam Jafri (Birmingham, GB)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The EMBRACE trial demonstrated significantly improved survival with eribulin compared to physicians’ choice (13.1 vs 10.9 months (p = 0.041). Eribulin has been funded by the NHS in the UK for the management of locally advanced or metastastic breast cancer after at least two lines of treatment. We describe the UK experience of eribulin in this setting.

Methods

Data from 577 patients was analyzed on an individual patient basis from 14 different hospitals after institutional review board approval. Data was collected retrospectively using computerized records and chemotherapy records. Data was collated on: age, breast cancer characteristics, prior chemotherapy regimes, toxicity, PFS and OS. Statistical analysis was performed using SPSS.

Results

Data from 577 patients who received eribulin in specialist cancer centres, teaching hospitals and cancer units throughout the UK between 2011-2017 were included. The median age of patients was 56 (33-84). 447 were ER positive, 129 triple negative, 100 patients were Her2 positive, 1 unknown. The cohort was heavily pre-treated with eribulin being received on average 4thline (median (range 2-11)). The median number of eribulin cycles received were 4 (range 1-29). The OS of the cohort was 288 days (95%CI 260-315), triple negative patients had a worse outcome than ER/Her2 expressing patients (198 c.f. 278 days (p = 0.02)). Less heavily pre-treated patients (≤2 prior treatments) had significantly better survival (328 c.f. 264 days). Patients aged over 65 had better survival 325 c.f. 285 days. 11% experienced grade 3-4 neuropathy, 14% experienced nausea, 19% experienced G3-4 neutropenia, there were no treatment related deaths.

Conclusions

This real world data demonstrates that even in a heavily pretreated population eribulin was associated an OS approaching a year. Eribulin was well tolerated even in patients over 65 and is associated with better survival if used earlier in metastatic patients.

Legal entity responsible for the study

The authors.

Funding

Eisai.

Disclosure

M. Jafri: Advisory board: PharmaMar; Speaker fees: Roche, Pfizer, PharmaMar. H. Kristeleit: Advisory board: Amgen and Roche; Speaker fees: Eisai and Roche. S. Ahmed: Consultancy: Eisai, Novartis, Roche, Pfizer, MSD, AstraZeneca, Takeda. A. Borley: Consultancy: Eisai, Roche, Pfizer. P. Nightingale: Educational grant: Eisai for statistical support. D. Rea: Roche, Novartis, Diachi Sankyo, AstraZeneca, Eisai. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

314P - Eribulin as first- or second-line chemotherapy for advanced or metastatic HER2-negative breast cancer: a real-world prospective study

Presentation Number
314P
Lecture Time
12:45 - 12:45
Speakers
  • Masato Takahashi (Sapporo, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

A global phase III study confirmed the effect of eribulin mesylate (ERI) as third- or later-line chemotherapy on overall survival (OS) for advanced or metastatic breast cancer. Meanwhile, in Japan, ERI can be used as first- or second-line. However, limited reports can be found on time to treatment failure (TTF) and/or OS for ERI as first- or second-line therapy comparing to late-line therapy in clinical practice.

Methods

We conducted a prospective study in patients with inoperable or recurrent HER2-negative breast cancer starting in September, 2014. We enrolled a similar number of patients receiving ERI as first- or second-line therapy and those receiving ERI as third- or later-line therapy, and with follow-up planned for up to two years (ClinicalTrials.gov: NCT02371174). The data collected by November 2017 was analyzed. TTF and OS were estimated using the Kaplan–Meier method. Multivariate Cox regression was used to identify the factors influencing TTF and OS.

Results

We analyzed 634 patients. The mean age (± standard deviation) was 59.6 years (± 11.0), and 157 patients (24.8%) had triple-negative breast cancer. Of these patients, 319 received ERI as first- or second-line therapy and 315 as third- or later-line therapy. The median TTF (95% confidence interval [CI]) was 135 (121–164) and 119 (106–128) days, and the median OS (95% CI) was 555 (475–628) and 383 (342–459) days for first- or second-line- and third- or later-line therapy, respectively. A history of radiation therapy, complication of diabetes, liver metastasis, ECOG performance status, blood hemoglobin and aspartate aminotransferase levels at baseline, triple-negative breast cancer, and development of peripheral neuropathy after ERI treatment were significant factors influencing both TTF and OS.

Conclusions

Our real-world study showed patients with first- or second-line therapy of ERI have longer OS and TTF than those in third- or later-line therapy. These results suggested that patients with first- or second-line therapy of ERI have the potential for similar or more favorable outcomes from the ERI treatment compared with patients with third- or later-line therapy of ERI.

Clinical trial identification

NCT02371174, First release November 21, 2014.

Legal entity responsible for the study

Eisai Co., Ltd.

Funding

Eisai Co., Ltd.

Disclosure

M. Takahashi: Honorarium: Eisai, AstraZeneca, Pfizer. K. Inoue: Research funding (institutional): Eisai, Parexel, Puma Biotechnology, MSD, Novartis, GSK, Pfizer, Chugai Pharmaceutical, Daiichi Sankyo. Y. Sakata, H. Ikezawa, T. Matsuoka: Employee: Eisai Co. J. Tsurutani: Adviser: Eisai Co., Ltd. and Asahi Kasei Corporation; Honoraria: Eisai Co., Ltd., Taiho Pharmaceutical Co., Ltd., Roche Diagnostics K.K., Novartis Pharma, AstraZeneca K.K. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

315P - Prospective Cohort Study of Real World Chemotherapy Sequence for Metastatic Breast Cancer (KBCRN A001: E-SPEC Study)

Presentation Number
315P
Lecture Time
12:45 - 12:45
Speakers
  • Katsuhiko Nakatsukasa (Kyoto, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The prognosis for triple negative (TN) and hormone-refractory metastatic breast cancer (MBC) remains poor and treatment options are limited to cytotoxic agents. Furthermore, the optimal sequence of chemotherapy (CT) is unclear. In this prospective cohort study (E-SPEC), we observed optimal sequences of CT for improving long-term survival. This trial was registered with ClinicalTrials.gov (no. NCT02551263).

Methods

The study was conducted under a multi-institutional prospective observational design and involved patients with HER2-negative hormone-refractory MBC. Eligibility criteria were age 20-75 years; refractory to hormone therapy defined as TN type or recurrence during or within 6 months after the end of adjuvant treatment or refractory to at least one previous hormone therapy for MBC; and scheduled for first- and second-line CT after registration. All treatments were performed according to physician’s choice. Treatment regimens, efficacies and quality of life (QoL) were prospectively surveyed. Baseline data analysis included patient characteristics, real-world CT sequence of first- and second-line CT regimen and the reason for cessation of first-line CT.

Results

Between June 2015 and July 2017, a total of 201 patients were enrolled, 194 of whom were analyzed. Mean age was 58.9 years; 142 patients (73.2%) had ER- and/or PgR-positive disease; 52 patients (26.8%) had TN. Most frequent regimen for first- or second-line CT was eribulin (ERI) (88.9%) among patients who received second-line CT. Frequent sequences were oral fluorouracil (FU) followed by ERI (18.3%), bevacizumab/paclitaxel (Bev/PTX) followed by ERI (13.5%), and ERI followed by Bev/PTX (11.1%). Patients who received taxanes as first-line CT had significantly more adverse event discontinuation than those with oral FU or ERI (p < 0.01).

Conclusions

In this real-world setting, ERI was administered in almost all first- or second-line regimens and taxane-based regimens were associated with more adverse event discontinuations. We intend to further investigate overall survival among CT sequences, as well as progression-free survival, new metastasis-free survival, type of progression and QoL.

Clinical trial identification

NCT02551263.

Legal entity responsible for the study

Masakazu Toi.

Funding

Eisai.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

316P - Comparative effectiveness of nab-paclitaxel vs. paclitaxel monotherapy as first-line (1L) treatment of metastatic triple-negative breast cancer (mTNBC) in US clinical practice

Presentation Number
316P
Lecture Time
12:45 - 12:45
Speakers
  • Tricia Luhn (South San Francisco, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Taxanes are commonly used as a standard of care treatment for 1L mTNBC. Few studies have directly compared the effectiveness of nab-paclitaxel and paclitaxel in the real world setting, however. This study investigated the overall survival (OS) of nab-paclitaxel vs. paclitaxel as monotherapy in 1L treatment of mTNBC in routine practice.

Methods

A total of 200 patients in the Flatiron Health EHR-derived database were included based on a confirmed diagnosis of mTNBC from 1 Jan 2011 and 31 October 2016 and receipt of nab-paclitaxel or paclitaxel monotherapy as 1L treatment. The primary outcome, OS, was estimated by Kaplan-Meier methods and compared by the log-rank test and by univariate and multivariate Cox regression models. Time to next treatment (TTNT) was assessed as a secondary outcome.

Results

Compared with pts who received paclitaxel (n = 95), at baseline, those who received nab-paclitaxel (n = 105) were more likely to have been diagnosed at an earlier stage (I-III), have a treatment free ≤ 12 months (in pts with recurrent disease), adjuvant treatment with a taxane, a prior diagnosis of neuropathy and coverage by commercial healthcare insurance. Other characteristics were balanced between groups. Over 90% of pts with evaluable dosing data (179 of 195) received weekly doses of either taxane, with 100 mg/m2 as the most common dose for nab-paclitaxel and 80 mg/m2 for paclitaxel. Median OS was 11.2 months in pts treated with nab-paclitaxel and 10.8 months in paclitaxel-treated pts (log-rank P = 0.82). The OS hazard ratio (HR) from the adjusted Cox model was 0.90 (95% CI: 0.61, 1.32), indicating a similar risk of death between the two groups. The robustness of this result was confirmed in several sensitivity analyses. TTNT for nab-paclitaxel and paclitaxel was 4.7 and 4.3 months (log-rank P = 0.44), respectively, and did not differ in adjusted analyses (HR = 0.95 [95% CI: 0.65, 1.38]).

Conclusions

Nab-paclitaxel and paclitaxel monotherapy demonstrated similar outcomes, suggesting they may be considered interchangeable as 1L treatments for mTNBC.

Legal entity responsible for the study

F. Hoffmann-La Roche AG.

Funding

F. Hoffmann-La Roche AG.

Editorial Acknowledgement

Editorial assistance was provided by Health Interactions.

Disclosure

T. Luhn, S. Chui, A. Hsieh, P. Bajaj, W. Hasnain, T.G.N. Ton: Employee: Genentech, Inc. Stocks: Roche. J. Yi: Consulting agreement: AbbVie, Inc. A. Mecke, A. Falgas: Employee and stock owner: Roche. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

317P - Clinical efficacy of eribulin as first- or second-line treatment for patients with recurrent HER2-negative breast cancer: a phase II randomized study (JBCRG-19)

Presentation Number
317P
Lecture Time
12:45 - 12:45
Speakers
  • Ken-ichi Watanabe (Sapporo, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Anthracycline- or taxane-based regimens are the standard early-line chemotherapy for metastatic breast cancer. However, adverse effects of these treatments, such as neutropenia, peripheral neuropathy, edema, and alopecia, are a concern. The EMBRACE study has shown that eribulin is effective for metastatic breast cancer, even as a late-line treatment. The aim of this study was to investigate the usefulness of eribulin as first- or second-line treatment.

Methods

Patients with recurrent HER2-negative breast cancer who had received previous chemotherapy including both an anthracycline and a taxane were eligible for this phase II study. They were randomly allocated to receive eribulin or treatment of physician’s choice (TPC) as first- or second-line treatment. TPC was selected in advance from paclitaxel, docetaxel, nab-paclitaxel, and vinorelbine. The primary endpoint was progression-free survival (PFS). Secondary endpoints included time to treatment failure (TTF), response rate (RR), duration of response, and safety. (UMIN000009886).

Results

From May 2013 to January 2017, 72 patients were enrolled. The full analysis set comprised data from 58 patients (median age, 58 years; range, 33–82 years); 38 (65.5%) received first-line treatment and 20 (34.5%) received second-line treatment. 43 patients (74.1%) were ER- positive. The per protocol set comprised data from 57 patients. PFS, TTF, RR, and duration of response in both groups are shown in the table. The most common grade 3 or worse adverse events were neutropenia (6/27 [22.2%] in the eribulin group versus 5/31[16.1%] in the TPC group). The incidence of sensory neuropathy was low in both groups.

Eribulin (n = 26)TPC (n = 31)p-value
PFSMedian(M)6.6(5.0-8.1)4.2(0.8-7.6)0.273
TTFMedian(M)6.0(4.7-7.3)3.6(2.3-4.9)0.131
Tumor responseCR0(0.0%)0(0.0%)0.190
PR5(19.2%)6(19.4%)
SD16(61.5%)11(35.5%)
PD5(19.2%)13(41.9%)
ORR5(19.2%)6(19.4%)
Duration of responseMedian(M)3.0(2.1-3.9)2.8(2.4-3.3)0.794

Conclusions

Eribulin was not shown to be superior to TPC in terms of efficacy. However, patients in the eribulin group had slightly longer PFS and TTF.

Clinical trial identification

UMIN000009886.

Legal entity responsible for the study

Japan Breast Cancer Research Group (JBCRG).

Funding

Japan Breast Cancer Research Group (JBCRG).

Disclosure

K. Aogi: Honoraria: Chugai, Eisai, Sanofi, AstraZeneca, Taiho, Daiichi Sankyo, Ono, Otsuka, Nihon Medi-physics, Terumo, Becton Dickinson and Company; Research funding: Chugai, Eisai, Takeda and Sanofi. S. Ohtani: Speakers bureau: Chugai and Eisai. H. Kawaguchi: Honoraria: Chugai, AstraZeneca, Eisai, Kyowa-Kirin, Novartis, Taiho, Pfizer and Nippon Chemiphar; Consulting or advisory role: Chugai and AstraZeneca; Speakers bureau: Chugai, AstraZeneca, Eisai, Kyowa-Kirin, Novartis, Taiho, Pfizer and Nippon Chemiphar. S. Morita: Honoraria: Eisai and Taiho; Research funding: Eisai. N. Masuda: Honoraria: Chugai, Takeda, Pfizer and AstraZeneca; Research funding: Chugai, AstraZeneca, Kyowa-Kirin, MSD, Novartis, Pfizer, Eli-Lilly. M. Toi: Honoraria: Novartis, MSD, Takeda, AstraZeneca, Eisai, Genomic Health, Chugai, Taiho, Bayer, Eli Lilly, Daiichi Sankyo, Kiowa-Kirin, C&C Research Laboratories, Yakult, Sanofi, Shimadzu, Pfizer; Consulting or advisory role: Daiichi Sankyo, Kiowa-Kirin and Taiho; Research funding: Taiho, Chugai, Shimadzu, Astellas Phama, AFI technology and C&C Research Laboratories. S. Ohno: Speakers bureau: Chugai Pharmaceutical, Eisai, Pfizer, Novartis, Taiho, Kyowa-Kirin, AstraZeneca. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

318P - Clinical utility of hepatic arterial infusion chemotherapy for heavily pretreated metastatic breast cancer patients: A review of a single institution

Presentation Number
318P
Lecture Time
12:45 - 12:45
Speakers
  • Mitsuhiro Furuta (Shizuoka, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Liver metastasis is recognized as a risk factor for metastatic breast cancer (MBC). Hepatic arterial infusion chemotherapy (HAIC) is a treatment option for MBC in patients with extensive hepatic lesions; however, there is no standard regimen, and the effects have not been well discussed.

Methods

We reviewed our medical records of MBC to extract patients with resistance to standard systemic chemotherapies, critical liver metastasis, and who received HAIC with an FEM regimen (5-fluorouracil 333 mg/m2 [weekly], epirubicin 30 mg/m2 [every 4 weeks], and mitomycin-C 2.7mg/m2 [every 2 weeks]) in our institute.

Results

We identified 58 patients who received HAIC (median age at initiation, 58 [30-80] years) in our institute between 2002 and 2017. Their ECOG performance (PS) statuses were as follows: PS0, 44; PS1, 10; and PS 2, 4. Their receptor statuses were as follows: hormone receptor positive (HR+)/HER2+, 9; HR+/HER2-, 38; HR-/HER2+, 4; HR-/HER2-, 7. The median number of systemic regimens (including endocrine therapy) prior to HAIC was 6 (2-17). The median number of liver metastases was 8 (1-≥20); the median maximum size of liver metastases was 5.2 cm (1.6-20.1). The median number of extrahepatic metastatic site was 2 (0-5). The median overall survival (days) was as follows: overall, 371 (95% confidence interval [CI] 260-475); HER2+, 441 (95% CI 166-652); HER2-, 344 (95% CI 279-475). The median time to progression of intrahepatic lesions (days) was as follows: overall, 303 (95% CI 184-491); HER2+, 491 (95% CI 90-NR); HER2-, 298 (95% CI 184-387). An objective response (CR+PR) of intrahepatic lesions was observed in 37 patients (63.8%). The reasons for the discontinuation of HAIC included: progression of extrahepatic lesion(s), 20 (34.5%); progression of intrahepatic legion(s), 16 (27.6%); clinical progression, 7 (12.1%); transition to maintenance therapy, 6 (10.3%); catheter-related events, 5 (8.6%); and duodenal ulcer, 1 (1.7%).

Conclusions

HAIC with an FEM regimen offers an effective treatment for patients with liver metastasis from MBC that shows resistance to systemic therapy.

Legal entity responsible for the study

Junichiro Watanabe.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

319P - A randomized, open label, phase II study of prophylactic octreotide (OCT) to prevent/reduce the frequency and severity of diarrhea in patients (pts) receiving lapatinib (LAP) with capecitabine (CAP) for the treatment of metastatic breast cancer (mBC)

Presentation Number
319P
Lecture Time
12:45 - 12:45
Speakers
  • Peter Krivorotko (Saint Petersburg, RU)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The combination of LAP+CAP is approved for the treatment of pts with HER2+ mBC who progressed on prior therapy, which must have included anthracyclines, taxanes and trastuzumab. Octreotide long acting release (OCT) is approved for the treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid and vasoactive intestinal polypeptide-secreting tumors. Here we investigated the efficacy of the prophylactic use of OCT in the prevention or reduction of diarrhea associated with the treatment involving LAP+CAP.

Methods

Pts (N = 62) were randomized (1:1) to OCT (0.1mg/mL) + LAP (1250 mg/day) + CAP (2000 mg/m2/day) (n = 30) or LAP+CAP (n = 32), between 17-Dec-2014 and 13-Jan-2016. The primary objective was to determine the efficacy of prophylactic OCT in reducing the proportion of pts experiencing diarrhea with a severity of ≥grade 2 based on NCI-CTCAE version 4.03 during the first 3 cycles. The secondary objectives were ORR, CBR and other safety. Pearson chi-square test was used to compare the superiority of OCT+LAP+CAP arm with LAP+CAP arm.

Results

All pts enrolled in the study (database lock: 13-Feb-2018) were female with a median age of 56.5 years, and the majority was non-Hispanic or Latino (98%). Seven (23.3%) pts in the OCT+LAP+CAP arm and 9 (28.1%) pts in the LAP+ CAP arm had at least one episode of ≥grade 2 diarrhea within the first 3 cycles. The difference between the 2 arms was -4.8% with 95% exact CI: (-29.2%, 20.0%) and was not statistically significant (P = 0.775). The ORR and CBR in OCT+LAP+CAP vs LAP+CAP arms was 20.0% vs 18.7%, and 23.3% vs 28.1%, respectively. Two (7%) pts from OCT+LAP+CAP arm and 3 (9%) pts from LAP+CAP arm, died due to the disease under study. The most common all grade adverse events in OCT+LAP+CAP and LAP+CAP (>15% in either arm), respectively, were diarrhea (59% vs 45%), palmar-plantar erythrodysesthesia syndrome (45% vs 33%), rash (14% vs 21%), asthenia (7% vs 21%) and anemia (3% vs 18%).

Conclusions

Prophylactic use of OCT did not result in a lower incidence of ≥grade 2 diarrhea in mBC pts receiving LAP+CAP. No new safety issues were identified.

Clinical trial identification

NCT02294786.

Legal entity responsible for the study

Novartis Healthcare Private Limited.

Funding

Novartis Healthcare Private Limited.

Editorial Acknowledgement

Medical editorial assistance was provided by Sai Krishna Arepalli, PhD (Novartis Healthcare Pvt Ltd).

Disclosure

P. Krivorotko: Personal fees: Novartis, during the conduct of the study and outside the submitted work. J.P. Zarate, C. Babanrao Pisal, L. Smith: Employee: Novartis. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

320P - Nab-paclitaxel (nab-P) in mEtastatic bREast cancer (MBC) In elDerly patiEnts: a real life setting - NEREIDE Study

Presentation Number
320P
Lecture Time
12:45 - 12:45
Speakers
  • Vincenzo Adamo (Messina, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Elderly patients (pts) with MBC are under-represented in clinical studies and treatment is largely based on limited retrospective subgroup analyses. However, the 3 ESO-ESMO guidelines for Advanced Breast Cancer suggest that the management decisions should not be based on age alone.

Methods

This is an observational, retrospective, multicenter study conducted in 11 Oncology Sicilian Centers that evaluated safety and efficacy of nab-P in pts with HER2 negative MBC with age ≥ 65 years. We included 70 pts. Intrinsic molecular subtype: Luminal A (18.8%), Luminal B HER-2 negative (62.5%) and Triple negative (18.8%). The most common metastatic sites were: visceral plus bone (31.4%), bone (15.7%), lung (10%), visceral plus lymph nodes (10%). 33% of pts received nab-P as 4th line treatment. 87.1% of all pts received nab-P at doses 260 mg/m23-weekly and 12.9% received nab-P 125 mg/m2weekly. 28.6%, 25.7% and 26.2% of pts received previous treatment with taxanes in the neo-adjuvant and metastatic setting, respectively. Primary endpoint was safety of nab-P treatment. Secondary endpoints were overall response rate (ORR), progression free survival (PFS) and overall survival (OS).PFS and OS curves were estimated using the Kaplan-Meier method. ORR was defined as complete or partial response (CR+PR) according to RECIST 1.1 criteria. Adverse events (AEs) were assessed according to CTCAEv4.0.

Results

Median (m) age of pts who received nab-P: 67 years (65-83). mECOG PS: 1 (range 0-2). The m cycles administrated was 6 (range 1-21). 35.5% of pts had a dose reduction and 11.5% of pts had treatment interruptions due to toxicity. The most frequent AEs were G2-3 and were observed in 47% of pts. The main toxicities were fatigue (61.5%), neuropathy (53.8%) and leukopenia (39.1%) and occurred in the 85.7% of pts treated with 3-weekly nab-P. ORR was 31.3% (CR in 6.3% and PR in 25% of pts). 39.1% of pts reported a stable disease. mPFS was 6 months (95% CI 2-38) and mOS was 40.5 months (95% CI 7-255).

Conclusions

Our real-life study showed that the treatment with nab-P is an effective and well-tolerated regimen in MBC elderly pts, even if previously treated with other taxanes. In particular, our data indicate that the weekly nab-P can be safely administered in elderly MBC pts.

Legal entity responsible for the study

Vincenzo Adamo.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

321P - Response evaluation of cancer therapeutics in metastatic breast cancer to the bone: a single arm phase 2 study of whole-body magnetic resonance imaging

Presentation Number
321P
Lecture Time
12:45 - 12:45
Speakers
  • Michael Kosmin (Northwood, GB)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Accurate and reliable evaluation of response to systemic anti-cancer therapy (SACT) is fundamental in the management of metastatic breast cancer (MBC). CT and bone scans (BS) have significant limitations in assessing SACT response in bone disease in MBC, whereas whole-body magnetic resonance imaging (WB-MRI) shows significant promise. Published retrospective data show that the addition of WB-MRI to body CT alters treatment decisions in MBC. The primary objective of this study was to evaluate whether WB-MRI identifies progressive disease (PD) earlier than CT scans in patients with bone-only MBC.

Methods

Participants were enrolled when starting first or subsequent SACT for bone-only MBC, as established initially by BS and CT thorax, abdomen and pelvis. Baseline WB-MRI was performed within 2 weeks of trial entry. CT and WB-MRI were performed every 12 weeks until definitive PD was evident in one or both modalities. At PD, BS was assessed for bone disease progression. Radiologists independently reported CT, WB-MRI or BS and were blinded to the other modalities. Participant questionnaires were undertaken at weeks 12 and 36 to evaluate tolerability and satisfaction with WB-MRI and CT.

Results

Forty-five participants were enrolled, with a median time on-study of 24 weeks (range 1-84 weeks). Two patients were excluded due to unequivocal liver metastases on baseline WB-MRI; two had clinical progression before imaging PD; one was lost to follow up. Twenty-nine have had PD on imaging; eleven continue on-study. In 65.5%, PD was evident on WB-MRI only; 34.5% had PD on CT and WB-MRI concurrently; none had PD on CT only (McNemar’s test p < 0.0001). PD on BS was reported in 55.6% of cases of bone CT/MRI progression. Overall questionnaire response rate was 63.8%. No differences were found between CT and WB-MRI in levels of concern, comfort or pain at week 12 or 36. All participants reported satisfaction levels as ‘good’ or ‘very good’ for both modalities.

Conclusions

WB-MRI identifies PD before CT in most patients with bone-only MBC. Further studies will evaluate whether earlier identification of PD with WB-MRI and earlier SACT changes can lead to improved patient outcomes.

Clinical trial identification

NCT03266744.

Legal entity responsible for the study

East and North Hertfordshire NHS Trust.

Funding

Paul Strickland Scanner Centre.

Disclosure

M.-L. Ah-See: Consulting or advisory role: AstraZeneca, Novartis, Pierre Fabre, Merck Sharp and Domme; Honoraria: Roche. A. Marshall: Educational research grant: Bayer AG outside of this submitted work that was used in part to pay for salary for research undertaken. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

322P - Anti-tumor cell activity and in vitro profile of the next generation CXCR4 antagonist Balixafortide

Presentation Number
322P
Lecture Time
12:45 - 12:45
Speakers
  • Johann Zimmermann (Allschwil, CH)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Balixafortide is a very potent, well tolerated and highly selective next generation CXCR4 antagonist derived over the past decade through multiple rounds of optimization starting from the natural product polyphemusin. Clinical proof-of-concept was achieved in a Ph 1/2 study in combination with Eribulin in metastatic HER2-neg breast cancer. The anti-cancer effects and pluripotent action of Balixafortide may include sensitization of tumor cells to chemotherapy, suppression of metastatic spread, inhibition of angiogenesis, and activation of the immune system.

Methods

Balixafortide was tested in a HTRF-based CXCR4 ligand binding assay, in functional assays (Calcium flux and beta arrestin), and further profiled in a large panel of other receptors including CXCR7. Effects on tumor cell sensitization were followed with an intracellular pERK / pAKT signaling assay. Tumor cell migration was assessed by chemotaxis assays, and inhibition of angiogenesis was determined by HUVEC sprouting. Evidence for immune cell activation came from evaluation of corresponding marker such as interferon gamma. Balixafortide was in detail profiled in an extensive in vitro ADME panel.

Results

Balixafortide binds CXCR4 with high affinity (IC50 < 10nM). It blocks beta arrestin recruitment and Calcium flux with IC50s < 10nM. A high 1000-fold selectivity window was demonstrated in a large panel of receptors including CXCR7. Balixafortide potently inhibits pERK / pAKT signaling in the lymphoma lines Namalwa (IC50 < 200 nM) and Jurkat (IC50 < 400 nM). Balixafortide efficiently blocks SDF-1 dependent chemotaxis of MDA MB 231 breast cancer cells (IC50 < 20 nM), Namalwa and Jurkat cells (IC50 < 10 nM). Receptor occupancy wash-out studies with competitive antibody 12G5 revealed prolonged binding of Balixafortide to CXCR4. In addition, Balixafortide was optimized for favorable mouse and human ADME properties with balanced plasma protein binding, greater plasma and microsomal stability.

Conclusions

Balixafortide is a product of an extensive optimization process which started from polyphemusin and now represents a favorable balance between ADMET properties, potency and tolerability which allows high and frequent dosing of a CXCR4 antagonist in cancer patients.

Legal entity responsible for the study

Polyphor Ltd.

Funding

Has not received any funding.

Disclosure

J. Zimmermann: Employee and shareholder: Polyphor Ltd. T. Remus, G. Lemercier, D. Barker, D. Obrecht, G. Douglas, G. Gambino: Employee: Polyphor Ltd.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

323P - Subcutaneous trastuzumab (H SC) with intravenous pertuzumab (P IV) and docetaxel (D IV) in HER2-positive advanced breast cancer (BC): MetaPHER second interim analysis

Presentation Number
323P
Lecture Time
12:45 - 12:45
Speakers
  • Sherko Kümmel (Essen, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

H SC (Herceptin® SC) was approved based on the HannaH study (Ismael Lancet Oncol 2012). The single-arm, open-label MetaPHER study (NCT02402712) is the first large Phase IIIb study to evaluate the safety and tolerability of H SC + P IV (PERJETA®) + D IV as first-line treatment in patients (pts) with HER2-positive metastatic/locally advanced BC. Here, we report interim safety and preliminary efficacy.

Methods

Pts are ≥18-year-old females whose disease was not previously treated with systemic non-hormonal anticancer therapy. Pts receive 600 mg fixed-dose H SC q3w + 840 mg loading/420 mg maintenance P IV q3w + ≥6 cycles D IV q3w (>6 at investigator’s discretion; 75 mg/m2 initial dose) until disease progression (PD), unacceptable toxicity, withdrawal of consent, death or predefined study end. The primary endpoint is overall and cardiac safety and tolerability. Adverse events (AEs) are graded per NCI–CTCAE v4.0.

Results

Of 418 enrolled pts, 412 started study treatment; 330 (196 on treatment, 134 in follow-up [FU]) were on study by data cutoff (5 Jan 18). Median FU duration was 16.3 months. In the safety population 406/412 pts (98.5%) experienced ≥1 any-grade AE; 213 (51.7%) grade ≥3 AEs; 101 (24.5%) serious AEs (SAEs); and 86 (20.9%) AEs leading to P IV, H SC or D IV discontinuation. 47 pts (11.4%) died: 38 (9.2%) due to PD; 9 (2.2%) due to AEs; none from cardiac death. AEs of interest included grade ≥3 cardiac AEs (3 pts; 0.7%); ejection fraction decrease to < 50% and ≥10% points from baseline (32; 7.8%); investigator-reported administration-related and local injection-site reactions (80; 19.4%, including 19 [4.6%] with an AE related to H SC only). No MedDRA-preferred-term congestive heart failure was reported. 249/336 pts with baseline measurable disease had an objective response (74.1% [95% CI 69.1–78.7]). The clinical benefit rate was 81.1% (334/412 pts [95% CI 77.3–84.9]). 1-year progression-free survival was 63.1% (95% CI 58.4–68.2).

Conclusions

Safety and efficacy profiles of H SC + P IV as first-line treatment for pts with HER2-positive advanced BC were consistent with the known profiles for the H IV + P IV combination, and no new safety signals identified. The final analysis is planned for 2019.

Clinical trial identification

NCT02402712.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Editorial Acknowledgement

Support for third-party writing assistance for this abstract, furnished by Helen Keyworth, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Disclosure

S. Kümmel: Honoraria: Roche, Celgene, Novartis, Amgen and Daiichi Sankyo; Consultant/advisor: Roche; Travel/accommodations/expenses: Roche and Celgene. C.A. Tondini: Consultant/advisor: Myriad Genetics; Speakers’ bureau: Amgen; Travel/accommodations/expenses: Roche/Genentech, Novartis and Celgene. J. Abraham: Honoraria, including travel expenses for advisory roles: Novartis and Genomic Health. Z.I. Nowecki: Travel/accommodations/expenses: Roche/Genentech, Novartis and Amgen. A. Juarez: Honoraria, support for national and international congresses and clinical trials: Roche. F. Morales-Vásquez: Honoraria, educational grants and Speakers’ bureaus: Roche, AstraZeneca, Pfizer, MSD, Novartis, Teva and Eli Lilly. S. Cardona-Huerta: Honoraria for advisory and consulting/speaker roles: Roche. D. Heinzmann: Employee: F. Hoffmann-La Roche; Shares: Roche. J. He: Employee: F. Hoffmann-La Roche. A.N. Duc, A. Crepelle-Fléchais: Employee: F. Hoffmann-La Roche. M. Martín: Honoraria: Roche, Genentech, Novartis, Lilly and AstraZeneca; Research grants: Roche and Novartis. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

324P - Settings-Based Efficacy Comparison of Trastuzumab Biosimilars in Breast Cancer: A Systematic Literature Review

Presentation Number
324P
Lecture Time
12:45 - 12:45
Speakers
  • Hope S. Rugo (San Francisco, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

The US Food and Drug Administration (FDA) recently approved the trastuzumab biosimilar Ogivri™ (trastuzumab-dkst) for treatment of breast cancer based on physicochemical and functional biosimilarity and phase 3 efficacy and safety data in metastatic breast cancer (MBC). Clinical trials evaluating trastuzumab biosimilars for treatment of ERBB2-positive breast cancer have assessed bioequivalence through comparative efficacy outcomes as neoadjuvant therapy for early-stage breast cancer (EBC) or first-line therapy for MBC. We conducted a systematic review to examine whether demonstrating bioequivalence in terms of efficacy is different in EBC vs MBC.

Methods

MEDLINE and conference abstracts were identified using the search terms “biosimilar” AND “trastuzumab” from 1 January 2013 to 14 March 2018. Abstracts and manuscripts were manually reviewed to assess availability of efficacy data comparing the proposed biosimilar with reference trastuzumab.

Results

A total of 84 results were obtained. After selection for studies with comparative clinical efficacy results, 8 phase 3 clinical trials for 6 proposed biosimilars were included in the final analysis: 4 in EBC (primary efficacy outcome, pathologic complete response [pCR]) and 4 in MBC (primary efficacy outcome, overall response rate [ORR]). In all trials, the proposed biosimilar was equivalent to reference trastuzumab in terms of efficacy. Two biosimilars (CT-P6 [2 different formulations], Celltrion, Incheon, Republic of Korea; PF-05280014, Pfizer, New York, NY) showed equivalent efficacy in both the EBC and MBC settings.

Conclusions

All biosimilars assessed demonstrated equivalent efficacy to reference trastuzumab, regardless of clinical setting. Two biosimilars demonstrated equivalent efficacy in both the EBC and MBC settings. Although the FDA and European Medicines Agency determine biosimilarity based on totality of evidence, both the EBC and MBC settings appear to have similar sensitivity and be appropriate for determination of equivalent efficacy based on regulatory guidelines and clinical results. Together, these data support extrapolation between settings.

Legal entity responsible for the study

Mylan Inc.

Funding

Mylan Inc.

Editorial Acknowledgement

Editorial assistance was provided under the direction of the authors by Tyler Rork, PhD, and Jennifer Rossi, MA, ELS, MedThink SciCom, with support from Mylan Inc.

Disclosure

H.S. Rugo: Travel, accommodations, expenses: Puma Biotechnology, Mylan, Lilly, Pfizer, Merck, Amgen, Teva research funding (all to the UC Regents): Merck, Pfizer, Lilly, Novartis, Macrogenics, Eisai, Genentech/Roche, OBI Pharma. G. Curigliano: Speaker fees: Pfizer, Novartis, Roche and Lilly. F. Cardoso: Consultant or advisor: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Seattle Genetics, and Teva. J. Cortes Castan: Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer; Consultant or advisor: Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, and Merus. E. Pennella, R. Muniz: Employee of Mylan Inc. and may hold stock with the company. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

325P - Pertuzumab, Trastuzumab and Taxane combination for Visceral Organ Metastatic Patients: Real Life Practice Results

Presentation Number
325P
Lecture Time
12:45 - 12:45
Speakers
  • Ece Esin (Ankara, TR)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Anti-HER2 agents were a breakthrough in the treatment of HER2-enriched breast cancer (BC). In this study, we aimed to describe the real-life efficacy and safety of pertuzumab-trastuzumab-taxane (PTT) combination in BC patients.

Methods

This study was conducted by the Turkish Oncology Group and reached 35 centers nationwide. 309 visceral metastatic, and trastuzumab naive patients who received first line PTT were included.

Results

Patients' characteristics and treatment details are summarized in the table. Median progression-free survival (PFS) was 28.5 months (95% CI:15.6-41.4), while median overall survival (OS) was 40.3 months (95%CI: 26.9-53.7). Brain metastatic patients (n = 13, 4.2%) had worse PFS (16.8m vs. 28.5m; HR:3.9, 95% CI:1.7-9.2, p = 0.002) and OS (26.7m vs. 40.3m; HR:3.2, 95% CI:1.3-7.6, p = 0.009). Elderly patients (>65y) had significantly lower OS results (19.8m vs. 40.3m; HR:0.4, %95 CI:0.2-0.8, p = 0.01). Docetaxel was the choice in 268 patients (86.7%), while 41 patients (13.3%) received paclitaxel. There was no statistically significant difference in PFS (28.5 m vs. 24.1 m; p = 0.61) and OS (40.3 m vs. NR; p = 0.17) between taxane groups. Additionally, ≥10 cycles of docetaxel were not associated with improvement in outcomes compared with 6-10 cycles. One treatment-related death due to sepsis was noted. In 8 patients (2.6%), 5-40% ejection fraction decrease from baseline was detected without any sign of heart failure.

Demographic characteristics and treatment details

N = 309%
Median age (year, range)51 (22-82)
>65 years-old patients3912.6
De-novo metastatic patients25883.5
Histopathology
IDC29093.9
ILC31
Mixt51.6
Others113.5
Hormone receptor status
ER and/or PR positive17055.2
ER/PR negative13844.8
Unknown10.3
Metastatic site distribution
Liver ± LN/skeletal11236.3
Lung ± LN/skeletal12038.8
Brain only61.9
Brain + liver + lung72.3
Liver + lung165.2
Other4815.5
Only skeletal or only LN--
Prior therapies
Prior anthracyclines5116.5
Prior trastuzumabNANA
Treatment details
Median number of cycle (range)
Pertuzumab-trastuzumab10 (1-75)
Docetaxel6 (1-23)
Paclitaxel3 (1- 26)

IDC: Invasive Ductal Carcinoma ILC: Invasive lobular carcinoma LN: Lymph Node

Conclusions

This real-life practice population differs from the CLEOPATRA study in terms of visceral only metastatic disease, and inclusion of brain metastatic patients. Regardless of these negative prognostic characteristics, results are concordant with the pivotal study. Elderly patients had overall lower PFS, which necessitates further investigation of pertuzumab-trastuzumab combination with cytotoxic/antihormonal therapies. To our knowledge, this is the largest scale real-life clinical practice study of PTT to date.

Legal entity responsible for the study

Ece ESIN, on behalf of Turkish Oncology Group.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

326P - Effectiveness of trastuzumab emtansine (TDM1) in patients with HER2-positive advanced breast cancer (ABC) progressing after taxane plus pertuzumab plus trastuzumab.

Presentation Number
326P
Lecture Time
12:45 - 12:45
Speakers
  • Benedetta Conte (Genova, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

In patients with HER2-positive ABC who were previously treated with taxane and trastuzumab without pertuzumab, TDM1 showed a progression free survival (PFS) of 9.6 months and an overall survival (OS) of 29.9 months. Paucity of data is available on the efficacy of TDM1 in patients progressing after the current standard first-line therapy in this setting, based on the association of a taxane plus trastuzumab and pertuzumab (i.e. the TPH regimen). The present study aims to evaluate the effectiveness of TDM1 after first-line TPH.

Methods

The Gruppo Italiano Mammella (GIM) 14/BIOMETA is a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with ABC. The present analysis was performed on patients who received second-line TDM1 after previous TPH between January 2012 and March 2017. Median PFS, 1-year OS (i.e. percentage of patients alive 1 year after the starting of TDM1) and clinical benefit rate (CB) were calculated. Descriptive statistics are reported with point estimated and 95% CIs. PFS was estimated with the Kaplan-Meier method.

Results

Out of 1858 patients included in the GIM14/BIOMETA study, 70 were eligible for the present analysis. Median age was 54 years; 36 patients (51%) had hormone receptor-positive/HER2-positive disease, and 27 (39%) had visceral involvement. All patients received TPH in the first-line setting, and 35 (50%) received taxane and trastuzumab in the adjuvant setting. At the time of data cutoff (April 30, 2018; median duration of follow-up 17.8 months), 30 patients (43%) were still receiving TDM1. Disease progression was the reason for treatment discontinuation in the remaining cases. Median PFS was 8.5 months (95% confidence intervals [CI] 5.3-12 months), and CB rate was 73%. One-year survival rate was 91%.

Conclusions

Our findings suggest that TDM1 is effective in patients progressing after TPH. A better performance was observed as compared to data previously published on TDM1 effectiveness after first-line TPH.

Clinical trial identification

NCT02284581.

Legal entity responsible for the study

Consorzio Oncotech.

Funding

Roche.

Disclosure

L. Del Mastro: Honoraria: Ipsen, Roche, Pfizer, Novartis, Eli Lilly, Eisai. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

327P - Survival of HER2-positive advanced breast cancer patients treated with lapatinib plus capecitabine – a national population-based study: long-term analysis.

Presentation Number
327P
Lecture Time
12:45 - 12:45
Speakers
  • Beata Jagielska (Warsaw, PL)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

In Poland, governmental policy was to offer a uniform, national therapeutic programme for the treatment of HER2-positive advanced breast cancer (ABC) patients (pts). Accordingly, the Polish Breast Cancer Treatment Programme was introduced. Herein, we present first results of this effort from the cohort of previously-treated patients who underwent anti-HER2 palliative therapy with lapatinib plus capecitabine.

Methods

The aim of the study was to assess the population-based value of lapatinib plus capecitabine therapy of HER2-positive ABC patients treated within the Polish Breast Cancer Treatment Programme during the years 2008-2015. Patients have been prospectively enrolled into aforementioned programme and treated according to the specified protocol. We used Kaplan-Meier method to evaluate progression-free survival (PFS), time to tumor progression (TTP) and overall survival (OS). The effects of clinical and demographic factors on PFS and OS were assessed using Cox’s proportional hazards regression model.

Results

A total of 1018 HER2-positive ABC women were enrolled into the Polish Breast Cancer Treatment Programme on a national level. Patients who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab were eligible to this study. Median age of the patients was 56.6 years (range, 22.8 to 86.1). Previous adjuvant therapy: 35.7% pts; ER(+)/PgR(+): 47.5% pts; number of metastatic sites ≥2: 45.9% pts. The median PFS was 6.4 months and median TTP was 6.7 months. The median OS was 11.76 months (range, 0.36-70.32). The overall response rate was 13%. Cox regression model data will be presented.

Conclusions

To our knowledge this study represents one of the first reports assessing the population-based value of a lapatinib/capecitabine treatment in clinical practice. Our data essentially corroborated findings obtained from randomized clinical trials. It seems that treatment with lapatinib and capecitabine is associated with a meaningful clinical effectiveness and therefore warrants consideration in the treatment algorithm of HER2-positive ABC patients.

Legal entity responsible for the study

Beata Jagielska.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

328P - Ribociclib (RIBO) + letrozole (LET) in premenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) with no prior endocrine therapy (ET) for ABC: Preliminary subgroup results from the phase 3b CompLEEment-1 trial

Presentation Number
328P
Lecture Time
12:45 - 12:45
Speakers
  • Hikmat Abdel-Razeq (Amman, JO)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

CDK4/6 inhibitor RIBO significantly improved progression-free survival in combination with ET versus placebo + ET in pre- and postmenopausal women with HR+, HER2– ABC and no prior therapy for advanced disease in the pivotal phase 3 MONALEESA-7 and MONALEESA-2 trials (Tripathy et al. SABCS 2018; Hortobagyi et al. NEJM 2016). Here, we report additional safety data for RIBO+LET in premenopausal female pts enrolled in CompLEEment-1, an open-label, phase 3b trial evaluating RIBO+LET as first-line therapy in an expanded pt population.

Methods

Premenopausal pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy, and no prior ET for ABC received RIBO (600 mg/day, 3 wk on/1 wk off) + LET (2.5 mg/day) and goserelin (3.6-mg subcutaneous implant every 28 days). The primary outcome was safety and tolerability. A pre-planned interim analysis was conducted ∼15 months after first pt first visit.

Results

Of the first 1,008 pts enrolled who completed 56 days of follow-up or discontinued before data cut-off, 153 were premenopausal women. Median age was 45.0 years and the majority of pts (99.3%) had an Eastern Cooperative Oncology Group performance status ≤1; 40.5% had stage IV disease at diagnosis. Bone (73.9%), lung (31.4%), and liver (30.7%) were the most common metastatic sites. The most frequent adverse events (AEs) were neutropenia (53.6%), nausea (30.1%), hot flush (20.9%), headache (17.0%), and asthenia (16.3%). The most frequent grade ≥3 AE was neutropenia (34.0%). QT prolongation was infrequent (2.0%). Dose adjustment/treatment interruption due to AEs was required for 48.4% of pts. Four patients (2.6%) discontinued treatment due to AEs.

Conclusions

Initial safety results from CompLEEment-1 demonstrate the tolerability of RIBO+LET + ovarian functional suppression in premenopausal women, consistent with previous reports. NCT02941926.

Clinical trial identification

NCT02941926.

Legal entity responsible for the study

Novartis Pharmaceuticals.

Funding

Novartis Pharmaceuticals.

Editorial Acknowledgement

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Elise Blankenship, PhD, ProEd Communications, Inc., for her medical editorial assistance with this abstract.

Disclosure

P.H. Cottu: Consulting or advisory role: Novartis and Pfizer; Travel, accommodations, expenses: Novartis, Pfizer, Roche; Honoraria: AstraZeneca, NanoString Technologies, Novartis, Pfizer, Roche; Research funding: AstraZeneca, Genentech/Roche, Novartis, Pierre Fabre, and Pfizer. A. Ring: Consulting or advisory role: Pfizer and Roche; Honoraria: AstraZeneca, Lilly, Novartis, Pfizer, Roche; Research funding: AstraZeneca. M. De Laurentiis: Consulting or advisory role: AstraZeneca, Celgene, Lilly, Novartis, Pfizer, Roche Honoraria: AstraZeneca, Celgene, Novartis, Pfizer, and Roche. J. Lu: Personal fees: Novartis; Personal fees from outside the submitted work; Syndex. H.A. Azim: Employment: Innate, France (immediate family member); Consulting or advisory role: AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Novartis, Pfizer, Roche; Honoraria: Amgen, AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche; Research funding: Pfizer. C. Zamagni: Consulting or advisory role: AstraZeneca, Eisai, Novartis, Pfizer, PharmaMar, Pierre Fabre, Roche; Travel, accommodations, expenses: Celgene, Novartis, Pierre Fabre, Roche; Research funding: AbbVie, Array BioPharma, AstraZeneca, Celgene, Medivation, Morphotek, Novartis, Pfizer, Roche, Roche/Genentech. K. Zhou, L. Menon: Employee: Novartis. J. Wu: Employee of Novartis; Employment: Janssen (immediate family member); Travel, accommodations, expenses: Janssen (immediate family member). M. Martín: Consulting or advisory role: Amgen, Lilly, Novartis, Pfizer, PharmaMar, Roche/Genentech; Research funding: Novartis. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

329P - Abemaciclib with fulvestrant in patients with HR+, HER2- advanced breast cancer (ABC) that exhibited primary or secondary resistance to prior endocrine therapy (ET)

Presentation Number
329P
Lecture Time
12:45 - 12:45
Speakers
  • Eva-Maria Grischke (Tuebingen, DE)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Abemaciclib, a selective inhibitor of CDK4 & 6, dosed on a continuous schedule is approved for the treatment of HR+, HER2- ABC. In the intent-to-treat population, abemaciclib with fulvestrant (F) demonstrated improved progression-free survival (PFS) and objective response rate (ORR) compared to placebo (P) + F (16.4 vs 9.3 mos, HR: 0.553; P<.0000001; ORR in measurable disease 48.1 vs 21.3%; P<.001). ET resistance (ETR) were classified into primary ETR, which includes pts whose disease relapsed while receiving the first 2 years of (neo)adjuvant ET or progressed while receiving the first 6 mos of ET for ABC, and secondary ETR. Here, we compare the efficacy and safety of abemaciclib + F vs P + F in the primary and secondary ETR subgroups.

Methods

MONARCH 2 was a phase 3 randomized, double-blind, placebo-controlled study of abemaciclib + F vs P + F in pts with HR+, HER2- ABC that progressed on ET. Key eligibility criteria were previously discussed. Pts received orally administered abemaciclib 150 mg Q12H + 500 mg F (per label) or P + F. Pts were stratified by sensitivity to ET. Primary objective was investigator-assessed PFS. Secondary objectives included efficacy, safety and tolerability.

Results

169 pts (25.3%) had primary ETR and 489 pts (73.1%) had secondary ETR. Key efficacy endpoints are summarized (Table). The most frequent adverse events in primary and secondary ETR population are similar. For primary ETR, abemaciclib + F vs P + F were diarrhea (87.3 vs 22.4%), neutropenia (43.6 vs 5.2%), nausea (41.8 vs 25.9%), abdominal pain (36.4 vs 13.8%), and anemia (31.8 vs 5.2%), respectively.

Summary of PFS and ORR in primary and secondary ETR population

Primary Resistance
Secondary Resistance
Abemacilib + FPlacebo + FAbemacilib + FPlacebo + F
PFS
Median (months)15.37.916.69.6
Hazard Ratio [HR] (95% CI)0.45 (0.31, 0.67)0.59 (0.46, 0.75)
Pvalue<.001<.001
ORR in measurable disease, (%)53.917.946.222.6
Pvalue<.001<.001

Conclusions

Abemaciclib + F improved PFS and ORR in pts with primary and secondary ETR, and had a generally tolerable safety profile. Although pts with primary ETR typically have poor prognosis the benefit for abemaciclib + F was maintained in pts HR+, HER2- ABC.

Clinical trial identification

NCT02107703.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

Y. Lin: Employee and stakeholder: Eli Lilly and Company. All other authors have declared no conflicts of interest.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

330P - Tamoxifen (TAM) or a non-steroidal aromatase inhibitor (NSAI) with ribociclib (RIB) in premenopausal patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): MONALEESA-7 subgroup analysis

Presentation Number
330P
Lecture Time
12:45 - 12:45