Abstract B005: Prognostic impact of BRCA1/2 mutational sites in a Brazilian cohort of ovarian cancer patients

Abstract Introduction: BRCA1 and BRCA2 genes are composed of distinct functional domains, but the extent to which mutations in specific regions impact treatment response or prognosis in ovarian cancer remains uncertain. The aim of this study was to investigate the prognostic relevance of BRCA1 and BRCA2 mutations according to their location in a cohort of patients with ovarian cancer. Methods: We retrospectively analyzed data from patients with ovarian cancer carrying pathogenic or likely pathogenic mutations in BRCA1 or BRCA2, treated at a tertiary cancer center in Brazil between 2016 and 2023. Mutations were classified into three groups based on their location: Group A included BRCA1 mutations upstream of the DNA-binding domain (DBD) (amino acids 39–284); Group B comprised BRCA1 mutations within or downstream of the DBD (amino acids 515–1837); and Group C included all pathogenic BRCA2 mutations. Overall survival (OS) and progression-free survival (PFS) were defined as the time from diagnosis to death from any cause and to disease progression or death, respectively. Results: Among 375 patients tested for BRCA1/2 mutations, 73 (19.4%) harbored pathogenic or likely pathogenic variants. The median age at diagnosis was 54.2 years; 21.6% were FIGO stage I–II, and 66% were stage III–IV. A personal history of breast cancer was reported in 8.5% of patients, while 38.9% had a family history of breast or ovarian cancer. PARP inhibitor maintenance therapy was administered to 110 patients (29.3%), either in the first-line setting or at recurrence. Patients with Group A (93.3%) and Group C (100%) mutations were more likely to present with FIGO stage III or IV disease compared to those in Group B (73.8%) and BRCA wild-type patients (68.1%) (p = 0.019). No significant differences were observed between mutational groups regarding age, personal history of breast cancer, or family history. After a median follow-up of 89 months, PFS did not differ across groups (median PFS: 31.9, 33.2, 39.2, and 39.1 months for wild-type, A, B, and C, respectively; p = 0.92), nor did OS (p = 0.98). Conclusions: In this cohort, the classification of BRCA1 and BRCA2 mutations based on their genomic position did not correlate with differences in survival outcomes. However, mutations located upstream of the BRCA1 DBD and in BRCA2 were more frequently associated with advanced-stage disease at diagnosis. These findings highlight the need for larger, multi-institutional studies to better understand the clinical implications of BRCA mutation site in ovarian cancer. Citation Format: Celso Silva. Sousa, Debora GAR. Souza, Artur LR. Bezerra, Luanna MS. Oliveira, Lurick R. Soares, Glauco Baiocchi, Louise B. Andrade, Andrea PG. Guimaraes, Elizabeth S. dos Santos, Alexandre André BA. da Costa. Prognostic impact of BRCA1/2 mutational sites in a Brazilian cohort of ovarian cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B005.