Genetic patterns and clinical associations of BRCA1 and BRCA2 mutations in familial and hereditary breast cancer: a cross-sectional study from Surakarta, Central Java.

Background Pathogenic variants in BRCA1 and BRCA2 are key determinants of hereditary breast cancer risk. However, data describing mutation patterns and their clinical associations in Southeast Asian populations remain scarce. Regional differences in genetic background and healthcare access may influence both mutation prevalence and phenotype. This study aimed to characterize BRCA1 and BRCA2 mutation patterns and evaluate their associations with demographic and clinicopathological features among patients with familial and hereditary breast cancer in Surakarta, Central Java, Indonesia. Methods A cross-sectional study was conducted at Dr. Moewardi Hospital, a tertiary referral center in Surakarta, between January 2024 and May 2025. Eighty consecutive patients with histologically confirmed breast cancer and available peripheral blood samples were included. Genomic DNA was analyzed using next-generation sequencing to identify BRCA1 and BRCA2 variants. Variant pathogenicity was determined according to established clinical classification guidelines. Associations between mutation status and age, breast cancer subtype (triple-negative versus non–triple-negative), and family history of cancer were assessed using chi-square or Fisher’s exact tests, followed by logistic regression analysis. Statistical significance was defined as P  < 0.05. Results Pathogenic BRCA1/2 mutations were detected in 9 of 80 patients (11.25%), including 5 BRCA1 and 4 BRCA2 variants. Mutation prevalence did not differ significantly by age at diagnosis ( P  = 0.587) or breast cancer subtype ( P  = 0.847). In contrast, a significant association was observed between mutation status and family history of cancer ( P  = 0.0002). Patients with a family history of non–breast malignancies had markedly increased odds of carrying a pathogenic BRCA mutation (odds ratio 21.4; 95% confidence interval 2.6–175.9). Conclusions In this Indonesian cohort, BRCA1/2 mutations were strongly associated with family cancer history but not with age or tumor subtype. These findings emphasize the importance of comprehensive family-history assessment and support the integration of early genetic counseling into hereditary breast cancer evaluation in resource-limited settings. Trial registration Not applicable (cross-sectional observational study).