• Heidi D Nelson, Rongwei Fu, Bernadette Zakher, Miranda Pappas, and Marian McDonagh.
• Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Portland.
• JAMA. 2019 Sep 3; 322 (9): 868-886.

ImportanceMedications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects.ObjectiveTo update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women.Data SourcesCochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists.Study SelectionDiscriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects.Data Extraction And SynthesisInvestigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model.Main Outcomes And MeasuresProbability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality.ResultsA total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication.Conclusions And RelevanceTamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.

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