Pathologic complete response and survival according to germline BRCA1/2 status in triple-negative breast cancer

Abstract Background Germline BRCA1 / 2 pathogenic variants (g BRCA -PV) are associated with chemosensitivity in triple-negative breast cancer (TNBC), but whether higher pathologic complete response (pCR) rates translate into improved long-term outcomes remains uncertain. We assessed associations of g BRCA -PV status with pCR, recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) in a real-world TNBC cohort treated with neoadjuvant chemotherapy (NACT). Methods We retrospectively analyzed 293 patients with stage I-III TNBC diagnosed between 2007 and 2023 who were treated with NACT and underwent germline BRCA1 / 2 testing at a single tertiary center. Multivariable logistic and Cox regression models assessed pCR, RFS and BCSS. Results Of 293 patients, 56 (19.1%) carried g BRCA -PV. The overall pCR rate was 49.5% and was higher in carriers than noncarriers (73.2% vs. 43.9%, p<0.001). After adjustment for age at diagnosis, clinical stage, NACT regimen, noncarriers had lower odds of pCR (OR 0.36, 95% CI 0.18–0.70, p=0.004). In Cox models, associations between g BRCA -PV status and RFS or BCSS did not reach statistical significance, either with or without adjustment for pCR, and estimates were imprecise. pCR was strongly associated with improved RFS (HR 0.24) and BCSS (HR 0.20) (both p<0.001). Conclusions g BRCA- PV carriers were more likely to achieve pCR after NACT, whereas associations with RFS or BCSS remained uncertain. The limited number of events and wide confidence intervals preclude firm conclusions regarding survival differences. Larger cohorts with longer follow-up are needed to clarify the relationship between g BRCA status, treatment response and long-term outcomes.