Genetics of breast cancer

Mayo Clin Proc. 1997 Jan;72(1):54-65. doi: 10.4065/72.1.54.


Familial breast cancer is characterized by young age at diagnosis, an increased risk of bilateral breast cancer, an increasing risk in conjunction with increasing numbers of affected family members, and a strong association with ovarian cancer. At least eight candidate breast cancer susceptibility genes have been identified. Mutations in BRCA1, BRCA2, p53, and the Cowden disease gene are relatively uncommon, are highly penetrant, and produce striking familial clusters of breast cancer. BRCA1 and BRCA2 are the most important of these, accounting for an estimated 80% of hereditary breast cancer and 5 to 6% of all breast cancers. Specific BRCA1 and BRCA2 mutations are of particular importance in population subgroups, such as those identified among Jewish women of central European (Ashkenazi) origin. Mutations in the ataxia-telangiectasia gene and the rare HRAS1 variable number of tandem repeats polymorphisms are much more common but also much less penetrant. They do not produce dramatic familial aggregations of breast cancer but may prove to be responsible for a substantial proportion of all breast cancers if their epidemiologic association with breast cancer is confirmed. Predictive genetic testing for breast cancer risk is under way. Oncologists and primary-care physicians must become familiar with these genetic disorders and the issues surrounding predictive testing in order to make appropriate management decisions about women thought to have a high genetic risk of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia / genetics
  • Breast Neoplasms / genetics*
  • Disease Susceptibility
  • Female
  • Founder Effect
  • Genetic Linkage
  • Humans
  • Li-Fraumeni Syndrome / genetics
  • Point Mutation
  • Predictive Value of Tests
  • Risk Factors