High Prevalence of Germline Mutations in Cancer Susceptibility Genes in Thai Patients with Clinical Spectrum of Hereditary Breast-Ovarian Cancer Syndrome

Abstract Background: Germline genetic mutation plays a significant role in breast cancer susceptibility. The strength of such predisposition varies among ethnic groups across the globe, and clinical data from Asian population to develop a strategic approach to who should undergo a genetic test are lacking. Methods: We performed a multigene test with next generation sequencing in our 5-year hereditary breast-ovarian cancer spectrum cohort consists of 306 breast cancer patients, 62 ovarian cancer patients, 14 pancreatic cancer patients and 7 prostatic cancer patients. Results: There were 83 pathogenic/likely pathogenic (P/LP) variants identified in 104 patients, 44 of these P/LP variants were novel. We reported a high rate of germline P/LP variants in breast cancer (24%), ovarian cancer (37%), pancreatic cancer (14%), and prostatic cancer (29%). Germline P/LP variants in BRCA1 and BRCA2 accounted for 80% of P/LP variants found in breast cancer and 57% of P/LP variants found in ovarian cancer. The detection rate of NCCN 2019 guideline for genetic/familial high-risk assessment of breast and ovarian cancers was 22-40%. Conclusion: Overall, the data from this study strongly support the consideration of multigene panel test as a diagnostic tool for patients with hereditary breast-ovarian cancer spectrum in Thailand.