Neoadjuvant pembrolizumab plus chemotherapy in germline BRCA-mutated early triple-negative breast cancer: a multicenter real-world cohort.

Neoadjuvant pembrolizumab plus chemotherapy improves outcomes in early triple-negative breast cancer, but real-world evidence in patients with pathogenic BRCA1/2 variants remains limited. We analyzed 726 consecutively treated patients from the multicenter Neo-Real/GBECAM-0123 cohort who received at least one cycle of neoadjuvant pembrolizumab plus chemotherapy and underwent surgery. Patients with pathogenic BRCA1/2 variants (mBRCA) were identified in 105 of 600 tested patients (17.5%), corresponding to 14.5% of the overall cohort. Among mBRCA carriers, 82 (78.1%) had BRCA1 variants, 22 (21.0%) had BRCA2 variants, and in 1 patient (0.1%) the BRCA subtype was not specified. The comparator group comprised 621 patients with wild-type or unknown BRCA status (wt/unknown BRCA). Pathologic complete response was higher in the mBRCA group than in the wt/unknown BRCA group (74.0% vs 61.7%). With a median follow-up of 22 months, event-free and overall survival were favorable in both groups, with a non-significant trend toward improved event-free survival in the mBRCA group, particularly among patients with residual disease.