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

BRCA1, BRCA2

Pathogenic or likely pathogenic germline variants in predisposition genes, including BRCA1/BRCA2 and MMR genes

This retrospective cohort from the Korean National Cancer Center included 5,829 patients with cancer tested between 2006 and 2023 with BRCA1/BRCA2-only testing or multigene panel testing. Overall, 987 patients (16.9%) carried a pathogenic or likely pathogenic variant, with the highest detection rates in ovarian cancer (24.2%) and in patients meeting multiple reimbursement criteria (up to 39.3%). Among carriers, 78.3% received at least one post-test clinical action, ranging from 84.3% for BRCA1/BRCA2 to only 46.0% for mismatch repair genes. Of 1,384 initial variants of uncertain significance, 25 (1.8%) were reclassified as pathogenic or likely pathogenic, identifying 46 additional carriers.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The useful figure is the care gap: fewer than one in two MMR gene carriers had a documented action, versus more than four in five for BRCA1/BRCA2, pointing to weaker organisation of follow-up outside the breast-ovarian pathway. The cohort, 96.6% female, reflects this recruitment and says little about other indications. Reclassification of 1.8% of variants of uncertain significance argues for a structured patient recontact pathway.

Analysis by Dr Thibaut Benquey