2020 Volume 66 Issue 5 Pages 384-391
Hereditary breast and ovarian cancer (HBOC) syndrome is defined by pathogenic germline variants of BRCA1 or BRCA2 (BRCA1/2). Genetic testing for BRCA1/2 became prevalent in the last 10 years. Before then, clinical criteria were used to screen for familial breast cancer patients. In 2012, the Japanese HBOC Consortium established a nation-wide registration project for subjects who had undergone BRCA1/2 genetic testing. Approximately 4,000 subjects who underwent genetic testing for BRCA1/2 and over 700 carriers of the BRCA1/2 mutation were registered. The proband annual frequency for a pathological variant is approximately 20%. There are few hot-spots for BRCA1/2 pathogenic mutations in the Japanese population. The mutation with the highest frequency, p.Leu63Ter, was verified to be a Japanese founder mutation. Approximately 30% of carriers of the BRCA1/2 mutation underwent risk-reducing salpingo-oophorectomy. Testing with multi-gene hereditary cancer panels has been preferred to Sanger sequencing even for classical genetic counseling, and recently, apart from the diagnosis of HBOC, companion diagnostics or cancer panel testing and liquid biopsy have been used to predict responses to targeted molecular therapeutics. Thus, HBOC could be an incidental diagnosis received after searching for an effective drug. Considering this scenario, a new type of genetic counseling involving early introduction of anticipatory guidance in counseling for HBOC is required. Risk reduction surgeries and MRI in the follow-up for HBOC patients will be covered by medical insurance from April 2020. I am honored to have contributed to the trend by the establishment of a nation-wide registration system and the publication of a guidebook for HBOC.