Uptake of cascade tests in relatives of patients undergoing cancer precision medicine in Japan

Abstract Objective Secondary findings of cancer patients who have undergone cancer precision medicine have been reported; however, cascade test outcomes have not yet been reported in Japan. This study aimed to evaluate the uptake of genetic medicine in cancer patients with germline pathogenic variants (GPVs) and cascade test in their relatives in Japan. Methods Referral to genetic counseling, incidence of secondary findings presumed GPVs (PGPVs) and GPVs, and uptake of confirmative germline testing and cascade test were retrospectively analyzed in 862 patients who underwent comprehensive genomic profiling testing in June 2019 and December 2023, using the institutional criteria of cascade test eligibility. Results Among the 852 patients who underwent tumor-only tests, 95 (11.2%) displayed PGPVs, 54 (6.3%) visited genetic counseling, 34 (4.0%) undertook germline testing, and 22 (2.6%) showed GPVs. One GPV was detected in 10 tumor/normal-paired tests. The 23 detected GPVs included BRCA2 10, BRCA1 6, APC 1, ATM 1, BAP1 1, CDK4 1, CDKN2A 1, MSH2 1, and RAD51C 1. The 23 patients with GPVs had 43 relatives eligible for cascade test and 22 non-eligible relatives (including 9 young relatives aged 14–34 years). Cascade test was performed in 30 (69.8%) of the 43 eligible relatives, and GPVs were detected in 10 (33.3%). The median interval between GPV disclosure and cascade test was 50 days (range: 6–304 days). Conclusions The uptake level of cascade test can be acceptable. Hospitals need to maintain contact with the young untested relatives until they have achieved sufficient growth to undertake cascade test.