Abstract 231P
Background
HR+/HER2- subtype accounts for the majority of breast cancers occurring in germline BRCA1/2 mutation (gBRCAm) carriers. The prognosis and the best management of these patients compared to HR+/HER2- BRCA1/2 wild type (gBRCAwt) patients is largely unknown. We evaluated overall survival (OS) and progression-free survival (PFS) under first-line endocrine therapy (ET) or chemotherapy (CT) +/- ET among gBRCAm and gBRCAwt patients (pts).
Methods
ESME Metastatic Breast Cancer (MBC) database (NCT03275311), is a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. gBRCA status was defined in three groups (gBRCAm/BRCAwt/untested) at treatment initiation (baseline), or at any time (time-varying analysis).
Results
Among 13,776 HR+/HER2- MBC pts included in this analysis, 170 were gBRCAm, 676 gBRCAwt, and 12,930 untested at baseline. 46 and 124 gBRCAm pts respectively received 1st line ET and CT. Median OS and PFS are presented below, as well as a Cox model including gBRCA status as a time-varying variable, and adjusted on age, visceral metastases, metastatic sites number and metastasis-free interval. Table: 231P
| Time-varying analysis | Median OS | Time-varying analysis | ||||
| Median PFS | Adjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
| Overall Population | ||||||
| gBRCA m | 9.4 | 1 | 36.5 | 1 | ||
| gBRCA wt | 9.5 | 0.83 [0.71-0.97] | 0.017 | 40.6 | 0.79 [0.65-0.97] | 0.024 |
| gBRCA untested | 10.8 | 0.85 [0.73-0.98]] | 0.021 | 42.8 | 0.90 [0.75-1.08]] | 0.250 |
| Patients treated with 1st line endocrine therapy | ||||||
| gBRCA m | 6.9 | 1 | 38.7 | 1 | ||
| gBRCA wt | 10.3 | 0.63 [0.74-0.85] | 0.003 | 51.3 | 0.65 [0.43-0.97] | 0.037 |
| gBRCA untested | 11.4 | 0.69 [0.53-0.91] | 0.009 | 48.1 | 0.81[0.56-1.18]] | 0.273 |
| Patients treated with 1st line chemotherapy | ||||||
| gBRCA m | 9.5 | 1 | 34.9 | 1 | ||
| gBRCA wt | 9.1 | 0.92 [0.77-1.11] | 0.379 | 36.0 | 0.89 [0.71-1.13] | 0.350 |
| gBRCA untested | 10.5 | 0.90 [0.77-1.07] | 0.238 | 37.9 | 0.98 [0.79-1.21] | 0.844 |
Conclusions
In this large real life cohort of HR+/HER2- MBC pts treated in the pre-CDK4/6 inhibitors era, gBRCAm status is associated with a lower overall survival, and lower PFS under 1st line endocrine therapy whereas similar PFS is observed in patients treated with 1st line chemotherapy regardless of BRCA status.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
Roche, Pfizer, AstraZeneca, MSD, Eisai, Daiichi.
Disclosure
J. Frenel: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Principal Investigator: Novartis; Non-Financial Interests, Principal Investigator: Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Pfizer; Non-Financial Interests, Principal Investigator: Daiichi; Non-Financial Interests, Principal Investigator: MSD. S. Delaloge: Financial Interests, Institutional, Advisory Board: AZ; Financial Interests, Institutional, Invited Speaker: AZ; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Invited Speaker: Exact Science; Financial Interests, Institutional, Advisory Board: Isi Servier; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Invited Speaker: Seagen. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Novartis. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Chugai. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Mylan; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Netris Pharma; Financial Interests, Personal, Advisory Board: Novartis. All other authors have declared no conflicts of interest.