Chemotherapy type and survival in young BRCA1/2 carriers with HER2-negative early breast cancer

Background Evidence to guide (neo)adjuvant chemotherapy choices in carriers of germline BRCA1/BRCA2 pathogenic variants ( BRCA carriers) with early breast cancer (BC) is limited. We evaluated the association of different chemotherapy regimens with survival outcomes in this population. Methods The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, retrospective cohort study of BRCA carriers diagnosed with stage I-III BC at age ≤ 40 years, between 2000 and 2020. Disease-free survival (DFS) and overall survival (OS) were assessed among patients with HER2-negative disease treated with anthracycline-taxane, anthracycline-no-taxane, or non-anthracycline (neo)adjuvant chemotherapy. The association of platinum use with outcomes was evaluated in triple-negative breast cancer (TNBC). Results Among 4200 young BRCA carriers from 109 centres who received (neo)adjuvant chemotherapy for HER2-negative BC, 58.7% had TNBC. Median follow-up was 8.1 years (IQR, 4.7–12.6 years). Anthracycline-taxane, anthracycline-no-taxane, and non-anthracycline regimens were used in 74.4%, 19.3%, and 6.3% of patients, respectively. Platinum agents were administered in 19.8% of TNBC cases. After multivariable adjustment, no significant differences in DFS or OS were observed between anthracycline-no-taxane and anthracycline-taxane regimens (DFS adjusted hazard ratio [aHR] 0.88, 95% CI 0.73–1.05; OS aHR 1.20, 95% CI 0.87–1.67) or non-anthracycline regimens (DFS aHR 1.07, 95% CI 0.82–1.38; OS aHR 1.16, 95% CI 0.68–2.0). In TNBC, platinum use was not associated with improved outcomes. Conclusions In young BRCA carriers with HER2-negative early BC, no statistically significant differences in survival outcomes were detected across different chemotherapy regimens. Our findings may inform future prospective studies evaluating chemotherapy de-escalation strategies in this genetically defined population.