Factors affecting the implementation of cascade testing of patients with BRCA1 or BRCA2 pathogenic germline variants in Japan

In clinical management for hereditary cancer patients, risk assessment is needed not only for patients but also for their blood relatives. In people with Hereditary Breast and Ovarian Cancer syndrome (HBOC), benefits are demonstrated by identifying relatives with BRCA1 and BRCA2 pathogenic germline variants (PGV) and implementing clinical surveillance and risk-reduction surgeries for the at-risk organs. To date, the uptake of cascade testing has been reported to be insufficient, but only a limited number of studies have analyzed the barriers to cascade testing. The current study aimed to analyze the uptake of cascade testing in the relatives of Japanese HBOC probands and clarify the factors that promote cascade testing uptake. This retrospective study included 125 probands carrying BRCA1 or BRCA2 PGV and 425 of their first-degree relatives (FDRs). Individual clinicodemographic data were collected from medical records, and comparisons were made between those who did and did not undergo cascade testing. Ninety-two (21.6%) FDRs of HBOC probands underwent cascade testing. Approximately 70% of the relatives underwent testing within 6 months of the proband's genetic testing. Independent predictors of cascade testing of 425 FDRs were: being present at the proband's genetic counseling session [odds ratio (OR): 8.3, 95% CI 4.2–16.1], cost-free testing (OR: 2.4, 95% CI 1.4–4.2), being the child of a proband (OR: 1.9, 95% CI 1.1–3.2), and female sex (OR: 1.8, 95% CI 1.0–3.0). The cascade testing uptake rate of FDRs in this study was similar to or lower than other countries. cascade testing uptake can be improved in HBOC families by encouraging relatives (children, siblings, and parents) to attend genetic counseling with the proband. Further prospective studies are needed to pursue the reasons for accepting cascade testing, including an evaluation of intrafamily communication processes.