Mutational landscape of BRCA gene mutations in Indian breast cancer patients: retrospective insights from a diagnostic lab

Abstract Background Presence of Germline mutations in the BRCA 1 and BRCA 2 genes is the most significant epidemiological factor for breast cancer (BC), where germline BRCA1 (g BRCA 1) mutation increases the risk for BC by 59–87% and g BRCA 2 mutation increases the risk by 38–80%. In this retrospective study, we have analyzed NGS-based genetic data for samples received at our laboratory for genetic testing over a three-year period to understand the prevalence and pattern if any of BRCA 1 and BRCA 2 mutations in Indian breast cancer patients. Results BRCA gene sequencing using NGS was performed in 395 consecutive cases of BC referred for testing to our lab between 2021 and 2023. Genetic analysis of mutations BRCA 1 and BRCA 2 genes resulted in 115 (29%) positive patients. Out of 115 patients, 79 reported BRCA 1 mutations, whereas 36 had BRCA 2 mutations. Exon 10 (57. 3%) of BRCA 1 and exon 11 (52%) of BRCA 2 were the most mutated exons observed in this study. The c. 1961delA (26. 4%) variant, followed by the c. 68₆9delAG (22. 7%) variant in BRCA 1, and the c. 6373delA (20. 5%) variant in BRCA 2, were the most common mutations found in our study. Our data shows positive correlation of younger age group (20–45 years) with BRCA positive status (Chi-square p value = 0. 001). Conclusion BRCA mutation prevalence was 29. 1% in our data which is higher than Western countries. Based on our findings BRCA screening looks imperative for women with BC especially younger women (< 50 years), as family history based BRCA testing would miss out many BRCA positive candidates which could benefit from PARP therapy options.