• Heidi D Nelson, Miranda Pappas, Amy Cantor, Elizabeth Haney, and Rebecca Holmes.
• Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Portland.
• JAMA. 2019 Aug 20; 322 (7): 666-685.

ImportancePathogenic 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.ObjectiveTo 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 SourcesCochrane 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 SelectionDiscriminatory accuracy studies, randomized clinical trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer.Data Extraction And SynthesisData 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 MeasuresCancer 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.ResultsFor 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 RelevanceAmong 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.

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