Impact of Germline BRCA1/2 Mutations on Clinical Outcomes in Metastatic Triple-Negative Breast Cancer Patients Treated with Sacituzumab Govitecan-An International CEBCC Study from Poland, the Czech Republic and Slovakia.

Background: Germline breast cancer susceptibility gene 1/2 (BRCA1/2) variants guide breast cancer treatment, but their clinical relevance in metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) remains unclear. The study aimed to evaluate the association between BRCA status and outcomes in SG-treated mTNBC. Methods: We retrospectively analyzed 264 patients with mTNBC and known germline BRCA1/2 (gBRCA1/2) status who received SG between August 2021 and May 2025 across multiple oncology centers in Poland, the Czech Republic and Slovakia. Survival outcomes were compared between patients with gBRCA1/2 mutations (gBRCA1/2m) and those with gBRCA1/2 wild-type (gBRCA1/2wt) using Kaplan-Meier estimates, the log-rank test, and multivariable Cox proportional hazards models. Two-sided p < 0.05 was considered statistically significant. Results: Among 264 patients, 35 (13.3%) were gBRCA1/2m and 229 (86.7%) were gBRCA1/2wt. After a median follow-up of 9.9 months, the median progression-free survival (PFS) was 4.5 months (95% confidence interval [CI] 2.1-6.3) in gBRCA1/2 carriers versus 4.2 months (95% CI 3.5-5.8) in gBRCA1/2wt patients (p = 0.10). Median overall survival (OS) was 9.1 months (95% CI 5.0-15.1) in gBRCA1/2 carriers compared to 11.5 months (95% CI 10.3-13.5) in gBRCA1/2wt patients (p = 0.26). Brain metastases were more frequent in carriers (20% vs. 8.3%, p = 0.06). In multivariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status was the only independent predictor of poorer survival (hazard ratio 1.97, 95% CI 1.42-2.74, p < 0.01), while gBRCA1/2 status showed no independent association. Conclusions: In this large retrospective cohort of mTNBC patients treated with SG, the presence of gBRCA1/2 was not associated with statistically significant differences in PFS or OS.