Abstract
INTRODUCTION: Breast cancer remains the leading cause of cancer-related mortality among women worldwide, including Kazakhstan. Germline mutations in the BRCA1 and BRCA2 genes play pivotal roles in the pathogenesis of breast cancer, particularly in its aggressive subtypes. Despite the well-established impact of BRCA1-associated tumors on clinical outcomes, their specific characteristics within the Kazakhstani population remain insufficiently studied. This knowledge gap underscores the necessity for further research, including the present study. OBJECTIVE: To analyze the clinical, morphological, and molecular-biological features of BRCA1-associated breast carcinomas in Kazakhstani patients, with the aim of identifying more effective strategies for diagnosis and treatment. MATERIALS AND METHODS: This study included 86 female patients diagnosed with primary invasive breast cancer who received treatment at the Oncology Center in Astana between December 2023 and June 2024. This retrospective study was conducted at a single center. Molecular genetic testing was performed via next-generation sequencing to identify pathogenic variants in the BRCA1 gene. Clinical and pathological data were retrospectively extracted from patients' medical records. RESULTS: The mean age at diagnosis for patients with BRCA1-associated breast cancer was 44 years, which is 6 years younger than that of patients without BRCA1 mutations (50 years). BRCA1 mutation carriers more frequently presented with advanced-stage disease, higher histological grade, and elevated proliferative activity. The incidence of metastasis was significantly greater among BRCA1-positive patients (41.7% vs. 5.4%, p = 0.002). Compared with BRCA1-negative tumors, BRCA1-positive carcinomas exhibit markedly lower expression of estrogen and progesterone receptors, a molecular signature characteristic of triple-negative breast cancer. DISCUSSION: The findings of this study confirm that BRCA1-associated breast carcinomas are distinguished by distinct clinicopathological features, including early onset, aggressive biological behavior, and high-grade histology. These characteristics highlight the importance of personalized treatment and diagnostic strategies and underscore the need for tailored clinical risk assessments for Kazakhstani patients. CONCLUSION: This study revealed significant differences in the clinical and morphological characteristics of BRCA1-associated breast carcinomas among Kazakhstani women. These results provide a foundation for improving diagnostic and therapeutic approaches in Kazakhstan and for developing population-specific clinical guidelines.