Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

Abstract

The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations, suggesting the involvement of genetic component towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients. Among the 59 TNBC genomic DNA samples sequenced, 8 BRCA mutations were detected in 59 TNBC patients (13.6%). Almost 50% pre-menopausal TNBC patients had a BRCA mutation. Of the 8 BRCA mutations, we observed BRCA1 mutations in 6 TNBC patients, and BRCA2 mutations in 2 TNBC patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis in the observed cohort. Our data advocates that South Indian women with higher grade TNBC tumors and without hereditary breast and ovarian cancer should be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.

BRCA1 and BRCA2 mutations and their clinical relevance in selected women diagnosed with triple-negative breast cancer in Kenya: a descriptive cross-sectional study

“…In addition, their report indicated that most tumors were grade II or III, findings that were similar to those of our study. Furthermore, other studies observed the highest prevalence of BRCA1 mutant tumors in triple-negative breast cancer patients [ 22 , 23 ] similar to our findings. Age at diagnosis among the participants in this study was another important factor to note.…”

“…These findings are similar to those of Rajagopal et al . 2022 [ 22 ]. In addition, their report indicated that most tumors were grade II or III, findings that were similar to those of our study.…”

Whole exome sequencing for identification of specific gene mutations in an Indian cohort of triple- negative breast cancer patients

“…The LAR phenotype displays a high expression of AR and could act as a potential target in TNBCs. Mutations in the BRCA genes are also found to be frequently associated with advanced disease in TNBCs, especially among early on-set patients, and the prevalence of these mutations are typically higher ranging in our study from 20% and 26.6% for BRCA1 and BRCA2, respectively [50,51]. Apart from these driver mutations, our data reveals mutations in SLC7A8 (27%; 4/15), AMOT (20%; 3/15), CLEC11A (20%; 3/15), and ECHDC1 (13%; 2/15) genes with a q value of ≤ 0.1.…”