Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA pathogenic variant carriers and non-carriers: a multi-center retrospective cohort study in a Chinese population

Germline BRCA1/2 pathogenic or likely pathogenic variants (PVs) are well-established genetic risk factors for breast cancer. However, most previous studies focused on Western populations, leaving a gap in the characterization of Asian cohorts. Therefore, we conducted a retrospective analysis across three hospitals in Northwest China, aiming to elucidate the clinical implications of BRCA PVs in this understudied population. This multi-center, retrospective cohort analysis investigated the influence of BRCA PV status on the response to neoadjuvant chemotherapy (NAC) and prognosis. We enrolled 1009 stage I-III breast cancer patients who underwent germline BRCA1/2 testing and received at least four cycles of a standard NAC regimen between January 1, 2017, and August 31, 2025. The primary endpoint was pathological complete response (pCR), and the secondary endpoint was event-free survival (EFS). Of the 1009 patients, 62 (6.1%) carried BRCA1 PVs and 55 (5.5%) carried BRCA2 PVs. Overall, BRCA1 PV carriers had a higher pCR rate (50.0%) than non-carriers (35.5%), and this association persisted in multivariable analysis (OR = 1.88; 95% CI, 1.07–3.33; P = 0.030). BRCA2 -associated tumors showed a response comparable to sporadic tumors (27.3% vs. 35.5%). Although BRCA status was not associated with EFS in the overall cohort ( P = 0.148), among patients who didn’t achieve pCR, BRCA1 PV carriers had worse EFS ( P = 0.007). BRCA1 status is independently associated with a better NAC response, while its prognostic value in the overall cohort remains uncertain. Notably, BRCA1 PV carriers with residual disease exhibit worse EFS. These findings highlight the critical role of germline BRCA1/2 testing and provide evidence to inform personalized treatment strategies for a Northwest Chinese population.