369P - The impact of germline BRCA mutations in locally advanced, triple-negative breast cancer (TNBC) treated with platinum- based neoadjuvant chemotherapy

Background

Whether germline BRCA (gBRCA) mutation affects prognosis and whether it has implications on treatment decision in the neoadjuvant setting is unclear.

Methods

Two centers retrospective cohort study comprising all women with early-stage TNBC who completed genetic testing and were treated with neoadjuvant chemotherapy with dose-dense chemotherapy containing carboplatin, between 10.2014 and 3.2020. Clinico-pathological features and data on dose reduction and delays were collected. Data on outcomes including pathological complete response (pCR), overall-survival (OS) and disease-free survival (DFS) were also calculated. Differences of these variables by gBRCA status were investigated.

Results

Sixty-four 64 women were included in the final analysis, of which 31 had pathogenic gBRCA mutation and 33 were gBRCA wild-type. Clinico-pathological characteristics and dose density and intensity were similar between both groups. Among gBRCA mutated patients, 23/31 (74%) achieved pCR, compared to 17/33 (51%) in the non-mutated, p=0.035. At a median follow-up of 30 months, gBRCA mutated women had significantly favorable OS (HR=8.64, 95% CI 1.08-69.21, p=0.042) and a trend for a favorable DFS (HR=7.4, 95% CI 0.91-60.27; p=0.062). The favorable OS for gBRCA mutated women remained significant in multivariate analysis (p=0.029) and was noted regardless to pathological response (p=0.01).

Conclusions

Compared to non-mutated, gBRCA mutated women with locally advanced TNBC treated with neoadjuvant chemotherapy containing carboplatin had a higher pCR rate and better outcome. Whether gBRCA mutation has a role in deescalating treatment in this population, should be further investigated.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Goldvaser: Financial Interests, Personal, Speaker, Consultant, Advisor, Not related to the submitted work: Gilead, Oncotest , Novartis ; Financial Interests, Personal, Advisory Board, Not related to the submitted work: Pfizer; Financial Interests, Personal, Invited Speaker, Not related to the submitted work: Roche , AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD. R. Yerushalmi: Financial Interests, Personal, Speaker, Consultant, Advisor, outside the submitted work: Roche, Eli-Lilly ; Financial Interests, Institutional, Research Grant, outside the submitted work: Roche; Financial Interests, Personal, Advisory Board, outside the submitted work: Pfizer, Novartis, Gilead; Financial Interests, Personal, Invited Speaker, outside the submitted work: Medison, MSD, AstraZeneca. All other authors have declared no conflicts of interest.