Clinical Performance of International and Korean Genetic Testing Criteria for Hereditary Breast Cancer: A Large-Scale Cohort Analysis of 2,188 Individuals.

International guidelines, including the American Society of Breast Surgeons, American Society of Clinical Oncology-Society of Surgical Oncology (ASCO-SSO), and National Comprehensive Cancer Network (NCCN), have broadened the eligibility for germline testing in breast cancer (BC), whereas the Korean Health Insurance Review and Assessment Service (K-HIRA) criteria remain more restrictive. This study evaluated the prevalence of pathogenic variants (PVs) and compared the diagnostic yield of Korean versus international criteria in a high-risk hereditary BC cohort from a single-institution. We retrospectively analyzed 2,188 individuals referred for genetic counseling between January 2015 and June 2025. Germline testing included BRCA1/2 sequencing, multiplex ligation-dependent probe amplification, and multigene panels. Eligibility was determined according to the ASCO-SSO (Recommendation 1.1), NCCN (v3.2025), and K-HIRA. The prevalence, sensitivity, and number of missed cases of PVs were compared. PVs were identified in 178 (8.1%) patients. Among patients with BC (n = 1,796), 159 carried PVs (8.9%), 131 (82.4%) carried BRCA1/2, and 28 (17.6%) carried non-BRCA genes. Across the frameworks, the prevalence of PV among eligible patients was comparable (ASCO-SSO, 8.7%; NCCN, 9.5%; K-HIRA, 10.2%). The sensitivity differed (NCCN, 96.9%; ASCO-SSO, 92.5%; K-HIRA, 89.3%): the sensitivity of NCCN was significantly higher than that of K-HIRA (p = 0.001), whereas the differences were not significant for NCCN vs. ASCO-SSO (p = 0.071) and ASCO-SSO vs. K-HIRA (p = 0.336). Missed carriers were more frequent under K-HIRA (17/159, 10.7%) than under ASCO-SSO (12/159, 7.5%) and NCCN (5/159, 3.1%), and those missed by K-HIRA often had non-specific family histories (58.8%) or no family history (23.5%). In this cohort, K-HIRA criteria showed lower sensitivity than the international guidelines, leading to missed opportunities for prevention and treatment. Broader eligibility criteria and the integration of multigene testing may improve the detection of hereditary cancer and optimize clinical management in Korea.