Benefits and harms of breast cancer screening: A systematic review

Abstract

Importance Patients need to consider both benefits and harms of breast cancer screening. Objective To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy. Evidence Review We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO(to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, aswell as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes amongwomen at average risk of breast cancer (no knowngenetic susceptibility, family history, previous breast neoplasia, or chest irradiation).We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews. Findings Across all ages ofwomen at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-upwere similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95%CI, 0.73- 0.89]; Canadian Task Force: RR, 0.82 [95%CI, 0.74-0.94]; Cochrane: RR, 0.81 [95%CI, 0.74- 0.87]);were greater in ameta-analysis of cohort studies (RR, 0.75 [95%CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, amongwomen 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. Forwomen with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy resultwas higher (7.0%[95%CI, 6.1%-7.8%]) for annual compared with biennial (4.8%[95%CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy resultswere similar forwomen beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive resultswere lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancywas lowin quality. Therewas no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE. Conclusions and Relevance For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.