Real-World Germline Variant Landscape and Clinical Management in Korean Patients Tested for Suspected Hereditary Cancer.

Abstract

Germline pathogenic/likely pathogenic (P/LP) variants inform cancer treatment and prevention, yet real-world detection patterns and downstream clinical management remain poorly characterized in East Asian hereditary cancer cohorts. This retrospective cohort study included 5829 patients with cancer who underwent germline testing at the National Cancer Center, Republic of Korea, between April 2006 and April 2023 using BRCA1/2-only testing or multigene panel testing. We examined P/LP variant prevalence, detection patterns under the revised national reimbursement criteria, gene group-stratified post-test clinical management, and variant reclassification outcomes. Among 5829 patients (96.6% female; median age, 51 years), 987 (16.9%) carried P/LP variants. Detection rates differed across reimbursement criteria, with the highest rates in patients with ovarian cancer (24.2%) and those meeting multiple criteria (up to 39.3%). Among P/LP carriers, 773 (78.3%) received at least one post-test clinical action; however, action rates differed substantially across gene groups, ranging from 84.3% among BRCA1/2 carriers to 46.0% among mismatch repair gene carriers. Of 1384 initial variants of uncertain significance, 25 (1.8%) were reclassified as P/LP, identifying 46 additional carriers. Overall variant frequencies were strongly shaped by the breast and ovarian cancer-predominant cohort composition, whereas documented post-test clinical actions varied across gene groups. Variant reclassification identified additional P/LP carriers, supporting the need for structured recontact and follow-up pathways.