The impact of germline BRCA pathogenic variants in locally advanced, triple negative breast cancer treated with platinum-based neoadjuvant chemotherapy

• Published in: Breast cancer research and treatment 2024-06, Vol.205 (2), p.241-248
• Main Authors: Mutai, Raz, Kuchuk, Iryna, Goldshtein, Alexandra, Yerushalmi, Rinat, Rotem, Ofer, Maisel Lotan, Adi, Bdolah-Abram, Tali, Gabizon, Alberto, Goldvaser, Hadar
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast cancer; Carboplatin; Carboplatin - administration & dosage; Carboplatin - therapeutic use; Chemotherapy; Clinical Trial; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Female; Genetic screening; Germ-Line Mutation; Humans; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Neoadjuvant Therapy - methods; Neoplasm Staging; Oncology; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Prognosis; Retrospective Studies; Survival; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - mortality; Triple Negative Breast Neoplasms - pathology
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-024-07247-4

Background Whether germline BRCA (gBRCA) pathogenic variants (PV) affect 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 gBRCA PV (gBRCA carriers) 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 carriers (74.2%) compared to BRCA wild-type women (48.5%), p  = 0.035. At a median follow-up of 30 months, gBRCA carriers 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 carriers remained significant in multivariate analysis ( p  = 0.029) and was noted regardless of pathological response ( p  = 0.018). Conclusion Compared to wild-type, gBRCA carriers 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.