Molecular characteristics and prognostic insights into BRCA-associated breast cancer in Kazakhstan

TL;DR

This study examines BRCA-related breast cancer in Kazakhstan, finding distinct genetic patterns and survival differences that suggest personalized treatment approaches are needed.

Contribution

The first comprehensive analysis of BRCA1/2 mutations in Kazakhstani breast cancer patients, revealing genotype-phenotype correlations specific to this population.

Findings

BRCA1 mutations were associated with triple-negative breast cancer and poorer survival outcomes.

BRCA2 mutations were linked to hormone receptor–positive tumors but still showed worse progression-free survival.

BRCA1/2 mutation carriers presented with more advanced-stage disease compared to BRCA-negative patients.

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.

The online version contains supplementary material available at 10.1038/s41598-026-36086-0.

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