Abstract
Breast cancer remains the leading cause of cancer morbidity and mortality among women worldwide. Approximately 5-10% of cases involve pathogenic BRCA1/2 variants, typically associated with early-onset, aggressive disease. This study aimed to determine the frequency and spectrum of BRCA1/2 mutations among Kazakhstani breast cancer patients and to analyze their associations with clinicopathological features and survival outcomes. A total of 186 patients aged 21-90 years were examined between December 2023 and June 2024 using next-generation sequencing and retrospective chart review. The median age was 44 years for BRCA1, 48 for BRCA2, and 51 for BRCA-negative patients. Advanced disease (stages III-IV) was more common among mutation carriers (p < 0.001). Pathogenic BRCA1 and BRCA2 variants were found in 22% and 9% of cases, respectively; BRCA1 tumors were predominantly triple-negative (88%), whereas BRCA2 tumors were mainly hormone receptor-positive (65%). Both subtypes were largely poorly differentiated (61% and 53%, respectively). The median progression-free survival was 34, 12, and 8 months for BRCA-negative, BRCA1-, and BRCA2-positive groups, respectively (p = 0.001). To our knowledge, this is the first comprehensive analysis of BRCA1/2 mutation profiles among Kazakhstani women, highlighting distinct genotype-phenotype correlations and supporting the need for personalized therapeutic strategies in this population.