Current Status and Challenges of BRCA1 and BRCA2 Genetic Testing for Hereditary Breast and Ovarian Cancer in Japan

In patients with breast cancer, breast cancer gene 1 and 2 (BRCA1/2) genetic testing is used to diagnose hereditary breast and ovarian cancer (HBOC) and guide appropriate risk management for patients and their relatives. In Japan, this testing has been covered by the national health insurance system since 2020 for patients with breast cancer who meet specific eligibility criteria. However, insufficient implementation of genetic testing may lead to missed opportunities for appropriate risk-reducing strategies and early clinical intervention in patients with pathogenic variants. Therefore, we retrospectively evaluated the implementation status of BRCA1/2 testing and the prevalence of pathogenic variants at our institution.

We analyzed 354 patients with breast cancer who underwent insurance-covered BRCA1/2 genetic testing between July 2018 and September 2024. Patients were classified into three groups: a newly diagnosed group (diagnosed after the introduction of insurance coverage for HBOC testing in April 2020), a postoperative follow-up group (diagnosed before April 2020 and tested during follow-up), and a companion diagnostic group for metastatic breast cancer. Clinicopathological characteristics, fulfilled eligibility criteria, and positivity rates were compared.

Of the 354 patients, 238 (67.3%) were newly diagnosed, 60 (16.9%) were in postoperative follow-up, and 56 (15.8%) underwent companion diagnostic testing. Overall, 43 patients (12.1%) harbored pathogenic BRCA1/2 variants (BRCA1, n=21; BRCA2, n=22). Variant positivity rates were 10.1% in the newly diagnosed group, 20.0% in the postoperative follow-up group, and 12.5% in the companion diagnostic group.

The higher prevalence of pathogenic BRCA1/2 variants in the postoperative follow-up group suggests that genetic testing for hereditary breast and ovarian cancer (HBOC) may be underutilized among eligible breast cancer patients during follow-up. Proactive testing recommendations by healthcare providers and improved patient understanding are essential.