Association of BRCA Mutation Status with Clinical Outcomes in High-Grade Serous Ovarian Cancer

Background/Objectives: High-grade serous ovarian carcinoma (HGSOC) is associated with high relapse rates despite aggressive multimodal treatment. BRCA mutations, present in a substantial subset of patients, confer homologous recombination deficiency and increased sensitivity to platinum-based chemotherapy. This study evaluated the association between BRCA mutation status and clinical outcomes, focusing on dissemination patterns, treatment allocation, perioperative parameters, and progression-free survival (PFS). Methods: This prospective single-center cohort included 133 consecutive patients with newly diagnosed HGSOC treated between January 2020 and December 2025. Primary treatment strategy (primary debulking surgery [PDS] or neoadjuvant chemotherapy [NACT]) was determined by multidisciplinary assessment. BRCA testing was performed using tumor tissue or germline analysis. Patients were followed for 24 months. PFS was analyzed using Kaplan-Meier estimates and Cox regression models. Results: Pathogenic BRCA mutations were identified in 39.1% of patients. BRCA-mutated tumors demonstrated significantly lower rates of peritoneal carcinomatosis (50% vs. 77.77%, p = 0.001) and were more frequently managed with PDS (59.6% vs. 41.8%, p = 0.048). Perioperative outcomes were comparable between groups. Disease progression occurred less frequently in BRCA-mutated patients (32.69% vs. 51.85%, p = 0.017). In univariate analysis, BRCA mutation was associated with a 48% reduction in progression risk (HR 0.52, 95% CI 0.27-0.99, p = 0.048). After adjustment for age, FIGO stage, and residual disease, BRCA mutation was not independently associated with progression (HR 0.57, p = 0.124), although a protective trend was observed, while residual disease remained a significant predictor. Conclusions: In this prospective cohort, BRCA mutation status was associated with distinct dissemination patterns and a significant reduction in progression risk in HGSOC. Although residual disease remained the strongest independent prognostic factor after multivariable adjustment, a trend toward improved PFS observed among BRCA-mutated patients supports the role of homologous recombination deficiency as a meaningful modifier of disease trajectory. These findings reinforce the clinical relevance of molecular stratification in the contemporary management of HGSOC.