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Clinical risk management of breast, ovarian, pancreatic, and prostatic cancers for BRCA1/2 variant carriers in Japan

Journal of Human Genetics volume 68, pages 517–526 (2023)Cite this article

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Abstract

Opportunities for genetic counseling and germline BRCA1/2 (BRCA) testing are increasing in Japan owing to cancer genomic profiling testing and companion diagnostics being covered by national health insurance for patients with BRCA-related cancers. These tests are useful not only to judge whether platinum agents and PARP inhibitors are indicated but also to reveal an autosomal-dominant inherited cancer syndrome: hereditary breast and ovarian cancer. In individuals with germline BRCA variants, risk of cancers of the breast, ovary, pancreas, and prostate is significantly increased at various ages of onset, but the stomach, uterus, biliary tract, and skin might also be at risk. For women with pathogenic BRCA variants, breast awareness and image analyses should be initiated in their 20s, and risk-reducing procedures such as mastectomy are recommended starting in their 30s, with salpingo-oophorectomy in their late 30s. For male BRCA pathogenic variant carriers, prostatic surveillance should be applied using serum prostate-specific antigen starting in their 40s. For both sexes, image examinations ideally using endoscopic ultrasound and magnetic resonance cholangiopancreatography and blood testing should begin in their 50s for pancreatic surveillance. Homologous recombination pathway-associated genes are also causative candidates. Variant pathogenicity needs to be evaluated every 6–12 months when results are uncertain for clinical significance. Genetic counseling needs to be offered to the blood relatives of the pathogenic variant carriers with suitable timing. We review the recommended cross-organ BRCA risk management in Japan.

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Funding

This work was supported in part by the Health Labour Sciences Research Grant Fund (#20EA1027 to RY), Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#20H03817 to TK), JSPS KAKENHI Grant (#JP17K16881 to AU), and Pfizer Global Medical Grants (#75519111 to AU).

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Author notes

  1. These authors contributed equally: Arisa Ueki, Reiko Yoshida, Takeo Kosaka, Hiroyuki Matsubayashi.

Authors and Affiliations

  1. Department of Clinical Genetics, The Cancer Institute Hospital of JFCR, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan

    Arisa Ueki

  2. Institute for Clinical Genetics and Genomics, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8555, Japan

    Reiko Yoshida

  3. Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Takeo Kosaka

  4. Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan

    Hiroyuki Matsubayashi

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  1. Arisa Ueki
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  2. Reiko Yoshida
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  3. Takeo Kosaka
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  4. Hiroyuki Matsubayashi
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All of the four authors contributed equally on literature survey, data collection and writing manuscript.

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Correspondence to Hiroyuki Matsubayashi.

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All four authors are members of the HBOC guideline committee at the time of manuscript submission.

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Ueki, A., Yoshida, R., Kosaka, T. et al. Clinical risk management of breast, ovarian, pancreatic, and prostatic cancers for BRCA1/2 variant carriers in Japan. J Hum Genet 68, 517–526 (2023). https://doi.org/10.1038/s10038-023-01153-1

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  • DOI: https://doi.org/10.1038/s10038-023-01153-1

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