Abstract PS3-01-17: Brca1/2 mutation status and its prognostic implications in breast cancer: a 10-year survival analysis in peru

Abstract Breast cancer is a heterogeneous disease with genetic, environmental, and lifestyle causes. Among the hereditary forms, mutations in BRCA1 and BRCA2 represent the main risk factors, accounting for approximately 20-25% of hereditary cases and 5-10% of all cases. These tumor suppressor genes maintain genomic stability through DNA repair; their mutations increase the predisposition to early-onset breast cancer, bilateral tumors, and ovarian cancer. The objective of this study was to characterize and compare the clinical, pathological, and survival profiles of Peruvian breast cancer patients according to BRCA1/2 mutation status, and to evaluate their prognostic impact on overall survival. METHODS: We included 1,446 breast cancer patients evaluated at INEN (2013-2020) under protocol INEN13-48. Genetic testing for BRCA1/2 was performed at City of Hope. Group comparisons by BRCA status were conducted using standard statistical tests. Propensity score matching (1:1) by age and clinical stage resulted in 242 matched patients. Ten-year overall survival was analyzed with Cox regression models, accounting for delayed entry. Results: A total of 1,441 breast cancer patients were analyzed based on BRCA mutation status (BRCA-negative, BRCA1+, and BRCA2+). Significant clinicopathological differences were observed between the groups. The median age at diagnosis was 41 years (range: 18-84). BRCA1 carriers were diagnosed at a significantly younger age (median: 39 years) than BRCA-negative and BRCA2 patients (p = 0.042). Clinical stage II was the most frequent in all groups (∼43%). Although no statistically significant differences were observed in stage distribution, stage IV was slightly more prevalent in BRCA2 (13.2%). Molecular subtypes differed significantly between groups (p < 0.001): BRCA1: Predominantly triple-negative tumors (85.4%) and BRCA2: Higher proportion of HR+/HER2- tumors (47.6%). Regarding tumor proliferation, a Ki-67 index ≥ 20% was observed in 100% of BRCA1 and BRCA2 patients, significantly higher than in BRCA-negative patients (80.6%, p < 0.001). The presence of a second cancer was more frequent in BRCA1+ (37.9%) and BRCA2+ (25.5%) patients compared to BRCA-negative individuals (13.9%, p < 0.001). The most common type was a second breast cancer (69.4% in BRCA1; 66.7% in BRCA2), and a notable proportion of ovarian cancer was found in BRCA1+ patients (25%). Survival analysis revealed that BRCA1+ patients had a significantly higher risk of death compared to BRCA-negative patients (HR = 1.83; 95% CI: 1.12-2.98; p = 0.016). Advanced clinical stage (III/IV vs. I/II) was associated with nearly a threefold increased risk of death (HR = 2.70; 95% CI: 1.65-4.41; p < 0.001), and the triple-negative subtype was associated with a significantly higher mortality risk (HR = 2.10; 95% CI: 1.19-3.68; p = 0.01). CONCLUSIONS: BRCA1 mutation carriers were diagnosed at a younger age and exhibited a more aggressive clinical and pathological profile, characterized by a predominance of the triple-negative subtype, high Ki-67 index, and G3 histological grade. Additionally, they presented a higher frequency of second cancers (37.9%), particularly breast and ovarian cancer. These findings highlight the importance of considering BRCA status in prognosis assessment and treatment planning for breast cancer patients. Citation Format: N. Valdiviezo, P. Mora, I. Otoya, M. Acosta, J. Herzog, S. Neciosup, T. Vidaurre, Z. Morante, C. Castañeda, H. Gómez, C. Rabanal, L. Reynaga, Y. Sullcahuaman, H. Guerra, M. Velarde, J. Cotrina, V. Acuña, S. Gruber. Brca1/2 mutation status and its prognostic implications in breast cancer: a 10-year survival analysis in peru [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-17.