Prevalence of Germline Mutations in Women with Breast And/or Ovarian Cancer in a Tertiary Care Center in Pune, India

In India, the incidence of breast cancer accounted for 1,78,361 cases, whereas ovarian cancer accounts for 45,701 cases, according to Globocan Report 2020. These cancers are known to have a hereditary basis, and >10% of them are associated with pathogenic BRCA1 and BRCA2 mutations. The prevalence of BRCA1 and BRCA2 varies across various Indian studies and is reported to be 2.9–28%. However, gene mutations other than BRCA1 and BRCA2 which are shown to increase the risk of hereditary breast and ovarian cancer (HBOC) are underreported. Objectives: The objective of this study was to estimate the prevalence of deleterious germline mutations among women with breast and/or ovarian cancer. Material and Methods: A cross-sectional study was conducted in the department of oncology at a super specialty hospital. Patients were enrolled based on the current National Comprehensive Cancer Network guidelines for genetic risk and evaluation of HBOC. Demographic and clinical information was extracted from the electronic medical records of the hospitals from 2018 to 2021. Next-generation sequencing (NGS) was performed on the extracted DNA using a custom capture kit and classified based on the American College of Medical Genetics. Results: A total of 94 patients suspected of having HBOC were examined for deleterious germline mutations. The median age of the patient was 46 years (range: 38–57 years). Breast and ovarian cancer patients constituted 64.9% and 35.1%, respectively. The overall mutation detection rate was 25.5%. The positive mutation detection rate was 26.2% and 24.2% in breast and ovarian cancer, respectively, whereas the variant of uncertain significance rate was 18.03% and 24.2%, respectively. Among the pathogenic mutations, BRCA1 was the most common mutation in women with breast cancer (81.3%). In ovarian cancer, it was 50%. BRCA2 mutation was more prevalent in ovarian cancer (50%). Conclusion: Our study reports a higher prevalence of germline BRCA1 and BRCA2 mutations in breast and ovarian cancer as compared to other studies. Genetic testing can be offered to high-risk women regardless of family history. This will be useful during diagnosis and help physicians in planning subsequent treatment.