Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force

Ann Intern Med. 2005 Sep 6;143(5):362-79. doi: 10.7326/0003-4819-143-5-200509060-00012.


Background: Clinically significant mutations of BRCA1 and BRCA2 genes are associated with increased susceptibility for breast and ovarian cancer. Although these mutations are uncommon, public interest in testing for them is growing.

Purpose: To determine benefits and harms of screening for inherited breast and ovarian cancer susceptibility in the general population of women without cancer presenting for primary health care in the United States.

Data sources: MEDLINE (1966 to 1 October 2004), Cochrane Library databases, reference lists, reviews, Web sites, and experts.

Study selection: Eligibility was determined by inclusion criteria specific to key questions about risk assessment, genetic counseling, mutation testing, prevention interventions, and potential adverse effects.

Data extraction: After review of studies, data were extracted, entered into evidence tables, and summarized by using descriptive or statistical methods. Study quality was rated by using predefined criteria.

Data synthesis: Tools assessing risks for mutations and referral guidelines have been developed; their accuracy, effectiveness, and adverse effects in primary care settings are unknown. Risk assessment, genetic counseling, and mutation testing did not cause adverse psychological outcomes, and counseling improved distress and risk perception in the highly selected populations studied. Intensive cancer screening studies are inconclusive. Chemoprevention trials indicate risk reduction for breast cancer in women with varying levels of risk, as well as increased adverse effects. Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.

Limitations: No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.

Conclusions: A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / prevention & control
  • Evidence-Based Medicine
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Counseling
  • Genetic Predisposition to Disease*
  • Humans
  • Medical History Taking
  • Mutation*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / prevention & control
  • Risk Assessment
  • Risk Factors