Journal of Clinical Oncology & Advanced Therapy

Abstract

Background: Breast Cancer (BC) is a leading cause of cancer mortality in women worldwide, with significant clinical, and genetic heterogeneity. While BRCA1 and BRCA2 are the most well-studied genes in hereditary breast and ovarian cancer (HBOC), non-BRCA genes, including CHEK2, TP53, ATM, PALB2, and RAD51C, also contribute to BC predisposition [1]. Moreover, the complexity of genetic risk assessment is further highlighted by the fact that many patients with no discernible family history also develop the disease [2]. To improve precision in diagnostics, genetic counselling and focus on targeted treatments, it is essential to comprehend both regional patterns in India and global trends.

Methods: We performed a retrospective analysis of clinical and genetic data from 382 BC patients who were tested between 2022 and 2025 at a tertiary care center in India. Variables included age at diagnosis, family history, molecular subtype, and germline variants across HBOC-related cancer predisposition genes. Retrospective analysis was performed using descriptive statistics. Comparative analysis was conducted with published cohorts from Asian, Caucasian, and American populations. Disease-free survival (DFS) was evaluated in a subset of BRCA1- and BRCA2-mutated patients treated with the PARP inhibitor olaparib.

Results: Pathogenic, likely pathogenic and variant of unknown significance - damaging (VUS-D) were identified in 17.3% (n=66), variant of uncertain significance (VUS) in 30.1% (n=115) and no detectable variants in 52.6% (n=201). Of the positive cases BRCA1 & 2 were most frequently altered genes 78% (n=51). Among the non-BRCA pathogenic variants concluded to 22% (n=15) of the total positive cases. 66 % of patients reported a family history of breast or ovarian cancer. Peak incidence occurred in the 40-to-60-year age group. Among olaparib-treated patients, BRCA2-mutated individuals demonstrated prolonged DFS with fewer recurrence events compared to BRCA1-mutated patients.

Conclusions: In addition to characterizing the genetic landscape of breast cancer in this cohort, family and with no family history correlation was found to be significant. Genomic molecular subtype distribution reflects international patterns, but non-BRCA mutations in patients with no family history highlights the need for broad panel testing. The prolonged DFS outcomes observed in BRCA2 mutated patients support the clinical utility of PARP inhibitors in real-world Indian settings and guide the development of mutation-specific therapeutic benefit and reinforces the importance of integrating germline genetic findings into individualized treatment planning. Such efforts are essential in advancing precision oncology in underrepresented populations.