The Impact of Germline BRCA Mutations in Locally Advanced, Triple Negative Breast Cancer Treated with Platinum Based Neoadjuvant Chemotherapy

Abstract

Abstract Background Whether germline BRCA (gBRCA) mutation affects prognosis of women with triple negative breast cancer (TNBC) and whether it has implications for treatment decisions in the neoadjuvant setting is unclear. Methods This is a retrospective two-center cohort study comprising all women with early-stage TNBC who have completed genetic testing and were treated with neoadjuvant dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin. All eligible patients treated between 10.2014 and 3.2020 were included. Data on clinico-pathological, pathological response, overall-survival (OS) and disease-free survival (DFS) were evaluated. Differences in clinico-pathological features and outcomes were analyzed according to gBRCA status. Results Sixty-four women were included in the final analysis, of which 31 had pathogenic gBRCA mutation and 33 were gBRCA wild-type. Clinico-pathological characteristics were similar between both groups. The odds for pathological complete response (pCR) were significantly higher in gBRCA mutated women (74.2%) compared to BRCA wild-type women (48.5%), 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). The difference in DFS did not reach statistical significance (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 of pathological response (p = 0.018). Conclusion Compared to wild-type, gBRCA mutated women with locally advanced TNBC treated with neoadjuvant chemotherapy containing carboplatin had a higher pCR rate and better outcomes. These results strengthen the contention that gBRCA status should be considered when tailoring treatment decisions in women with locally advanced TNBC.