Familial breast and ovarian cancers

Int J Clin Oncol. 2004 Aug;9(4):270-82. doi: 10.1007/s10147-004-0423-3.

Abstract

About 60% of familial breast and ovarian cancers in Japan involve germline mutations of the BRCA1 or BRCA2 ( BRCA1/2) genes. These genes contribute to genetic stability and DNA repair and act as tumor suppressor genes. Mutation analysis of the BRCA1/2 genes has improved our understanding of both common mutation patterns in Japanese patients and the clinicopathological features of BRCA1/2-related cancers. BRCA1-related breast cancers are characterized by poor prognosis, a low rate of estrogen receptor positivity, and histological predominance of solid-tubular carcinoma. BRCA1-related ovarian cancers are associated with a high frequency of serous adenocarcinoma and a good outcome. Further large-scale studies are needed to delineate genotype-phenotype relations and penetrance in BRCA1/2-related breast and ovarian cancers in Japan. The development of systems for clinical genetics in Japan, including genetic counseling, has led to the increased use of genetic testing for the clinical management of BRCA1/2-related cancers. Three options are available for carriers of BRCA1/2 mutations: intensive surveillance, chemoprevention, and prophylactic surgery. Studies done in other countries indicate that prophylactic surgery effectively prevents the development of breast and ovarian cancers in carriers of BRCA1/2 mutations. However, prophylactic mastectomy remains controversial in Japan, and now systematic intensive surveillance is generally performed for the prevention of breast cancer in women at high risk. Early detection of ovarian cancer remains challenging, resulting in increased acceptance of the need for prophylactic oophorectomy in women at risk. This review summarizes experimental and clinical findings about familial breast and ovarian cancers, including data on Japanese patients.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / therapy
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / therapy
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Counseling
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Germ-Line Mutation / genetics
  • Heterozygote
  • Humans
  • Japan
  • Medical History Taking
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / therapy
  • Risk Factors