Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force [Internet]

Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Aug. Report No.: 19-05251-EF-1.


Background: 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.

Purpose: To update the 2013 U.S. 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 controlled trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer.

Data Extraction: Data on study methods; setting; population characteristics; eligibility criteria; interventions; numbers enrolled and lost to followup; outcome ascertainment; and results were abstracted. Two reviewers independently assessed study quality.

Data Synthesis (Results): 103 studies (110 articles) 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 of 10 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve 0.68 to 0.96). No studies determined optimal ages, frequencies, or harms of risk assessment.

Twenty-eight studies indicated genetic counseling is associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. A RCT showed that population-based testing of Ashkenazi Jews detected more BRCA1/2 mutations than family-history based testing, while measures of anxiety, depression, distress, uncertainty, and quality of life were similar between groups; clinical outcomes were not evaluated. Twenty studies indicated breast cancer worry and anxiety were higher after testing for women with positive results and lower for others, and understanding of risk was higher.

No RCTs evaluated the effectiveness of intensive screening for breast or ovarian cancer in mutation carriers. In observational studies, false-positive rates, additional imaging, and benign biopsies were higher with MRI than mammography. In eight RCTs, tamoxifen (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.59 to 0.84; 4 trials), raloxifene (RR, 0.44 95% CI, 0.24 to 0.80; 2 trials), and aromatase inhibitors (RR, 0.45 95% CI, 0.26 to 0.70; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Adverse effects included venous thromboembolic events for tamoxifen and raloxifene; endometrial cancer and cataracts for tamoxifen; and vasomotor, musculoskeletal, and other symptoms for all medications. In observational studies, mastectomy was associated with 90 to 100 percent reduction in breast cancer incidence and 81 to 100 percent reduction in breast cancer mortality; oophorectomy or salpingo-oophorectomy was associated with 69 to 100 percent reduction in ovarian cancer; complications were common with mastectomy.

Limitations: Including only English-language articles and studies applicable to the United States; varying number, quality, and applicability of studies; and few studies of untested women previously treated for BRCA1/2-related cancer.

Conclusions: Risk assessment, genetic counseling, and genetic testing to reduce BRCA1/2-cancer incidence and mortality as a prevention service has not been directly evaluated by current research. Risk assessment with familial risk tools accurately identifies high-risk women for genetic counseling. Genetic counseling reduces breast cancer worry, anxiety, and depression; increases understanding of risk; and decreases intention for mutation testing, while testing improves accuracy of understanding of risk. The effectiveness of intensive screening is not known, but it increases false-positive results and procedures. Risk-reducing medications and surgery are associated with reduced breast and ovarian cancer, but also have adverse effects. Evidence gaps relevant to prevention remain and additional studies are needed to better inform clinical practice.

Publication types

  • Review

Grants and funding

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, 5600 Fishers Lane, Rockville, MD 20857; www.ahrq.govContract No. HHSA-290-2015-00009-I, Task Order No. 7 Prepared by: Pacific Northwest Evidence-Based Practice Center, Oregon Health & Science University, Mail Code: BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239; www.ohsu.edu/epc