Mutation matters: understanding ovarian cancer, its clinical impact with germline variants among Indian women

Abstract

Epithelial ovarian cancer is associated with hereditary genetic mutations. This study investigates the genetic landscape and clinical outcomes of epithelial ovarian cancer in Indian patients. Despite the clinical relevance, genetic testing remains underutilized in India, and data on non-BRCA mutations and variants of uncertain significance are limited. This ambispective observational study included 150 ovarian cancer patients from a tertiary center in India (2017–2024). Patients were categorized into four groups based on their genetic testing. results: BRCA pathogenic/likely pathogenic (P/LP), non-BRCA P/LP, variants of uncertain significance (VUS), and germline-negative. Clinical, surgical, and survival outcomes were analyzed. Among patients with germline findings (P/LP or VUS) ( n  = 100), BRCA1/2 variants accounted for 83%, non-BRCA variants 17%. Median progression-free survival was similar across groups (13.5–15 months), but overall survival showed a trend favoring non-BRCA P/LP group (77 months) (p -0.05). Germline-negative status was independently associated with a 50% lower progression risk compared to BRCA carriers (HR = 0.51, p  = 0.015). Age and ECOG performance status were significant predictors of overall and progression free survival. Premenopausal women had 19% reduction in progression but showed a threefold increased risk of death compared to postmenopausal women (p-0.015). Patients undergoing primary cytoreductive surgery had a 59% reduction in death (HR = 0.41, p  = 0.043). The study highlights the diverse genetic landscape of ovarian cancer in Indian patients and the clinical relevance of both BRCA and non-BRCA mutations. Broader genetic testing, including for variant of uncertain significance and non-BRCA genes, can guide personalized treatment and improve clinical outcomes in ovarian cancer. The findings suggest potential survival advantages in non-BRCA mutation carriers and emphasize the importance of genetic testing in ovarian cancer management.