Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan

Masami Arai,Chie Watanabe,Seigo Nakamura,Shiro Yokoyama,Tadashi Nomizu,Mayuko Inuzuka,Akihiro Sakurai,Megumi Okawa,Junko Yotsumoto,Mizuho Kita,Yoshinori Akama,Hiroyuki Nomura,Reiko Yoshida,Masayuki Sekine,Takayuki Enomoto

doi:10.1038/s10038-017-0355-1

Abstract

The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families. The mutation-positive rate was 19.7%. Variants of uncertain significance were found in 6.5% of all individuals subjected to genetic testing for BRCA1/2. Compared to the United States, Japan had a higher mutation-positive rate in most categories, except for the groups with male breast cancer. Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2 mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and 3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was not observed during the follow-up period. The nationwide registration system began last year and the system enables follow-up analysis in Japan.

Highlights

Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant inherited cancer susceptibility disorder caused by deleterious germline mutations in BRCA1Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Hokkaido, Japan or BRCA2 (BRCA1/2)
Based on the registered clinical data, we examined what types of cancer were frequently observed in Japanese BRCA1/2 mutation carriers, and intrinsic subtypes of breast cancers in BRCA1/2 mutation carriers based on ER, PgR, and HER2 status
Information is not available on how risk-reducing surgeries are performed under the present medical insurance system in Japan or on how many cases of risk-reducing surgeries are performed

Summary

Introduction

Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant inherited cancer susceptibility disorder caused by deleterious germline mutations in BRCA1. Starting in 2004, BRCA1/2 genetic testing became a part of laboratory examinations in Japan. Medical insurance does not currently cover the clinical practice of HBOC, including genetic testing for BRCA1/2, medical surveillance, and preventive surgeries. These procedures are not prevalent in routine clinical practice, and the clinical and pathological characteristics of HBOC in Japan remain unclear. International database systems such as CIMBA (the Consortium of Investigators of Modifiers of BRCA1/2) or

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Conclusion