Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

JAMA. 2019 Aug 20;322(7):666-685. doi: 10.1001/jama.2019.8430.


Importance: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers.

Objective: To update the 2013 US Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women.

Data sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013, to March 6, 2019, for updates; January 1, 1994, to March 6, 2019, for new key questions and populations); reference lists.

Study selection: Discriminatory accuracy studies, randomized clinical trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer.

Data extraction and synthesis: Data on study methods, setting, population characteristics, eligibility criteria, interventions, numbers enrolled and lost to follow-up, outcome ascertainment, and results were abstracted. Two reviewers independently assessed study quality.

Main outcomes and measures: Cancer incidence and mortality; discriminatory accuracy of risk assessment tools for BRCA1/2 mutations; benefits and harms of risk assessment, genetic counseling, genetic testing, and risk-reducing interventions.

Results: For this review, 103 studies (110 articles; N = 92 712) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies (n = 43 813) of 8 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve, 0.68-0.96). Twenty-eight studies (n = 8060) indicated that genetic counseling was associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. Twenty studies (n = 4322) showed that breast cancer worry and anxiety were higher after testing for women with positive results and lower for others; understanding of risk was higher after testing. In 8 RCTs (n = 54 651), tamoxifen (relative risk [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials), and aromatase inhibitors (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Mastectomy was associated with 90% to 100% reduction in breast cancer incidence (6 studies; n = 2546) and 81% to 100% reduction in breast cancer mortality (1 study; n = 639); oophorectomy was associated with 69% to 100% reduction in ovarian cancer (2 studies; n = 2108); complications were common with mastectomy.

Conclusions and relevance: Among women without recently diagnosed BRCA1/2-related cancer, the benefits and harms of risk assessment, genetic counseling, and genetic testing to reduce cancer incidence and mortality have not been directly evaluated by current research.

Publication types

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

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / prevention & control
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / prevention & control
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Counseling*
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Humans
  • Mutation*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / prevention & control
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / prevention & control
  • Risk Assessment