Systematic reviews as a 'lens of evidence': Determinants of benefits and harms of breast cancer screening

Abstract

This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15-25% in trials and 28-56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1-60% in trials and 1-12% in studies with a low risk of bias, and cumulative false-positive rates were lower with biennial than annual screening (3-17% vs 0.01-41%). There is no consistency in the reviews' conclusions about the magnitude of BC mortality reduction among women younger than 50 years or older than 69 years, or determinants of benefits and harms of mammography, including the type of mammography (digital vs screen-film), the number of views and the screening interval. Similarly, there was no solid evidence on determinants of benefits and harms or BC mortality reduction with screening by ultrasonography or clinical breast examination (sensitivity ranges, 54-84% and 47-69%, respectively), and strong evidence of unfavourable benefit-to-harm ratio with breast self-examination. The reviews' conclusions were not dependent on the quality of the reviews or publication date. Systematic reviews on mammography screening, mainly from high-income countries, systematically disagree on the interpretation of the benefit-to-harm ratio. Future reviews are unlikely to clarify the discrepancies unless new original studies are published.

Keywords: accuracy; benefits; breast cancer screening; false-positive; harms; mortality; overdiagnosis; systematic review.

Figure 1

Reproduced with permission from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA group, Preferred Reporting Items for Systematic Reviews and Meta‐Analyses: The PRISMA statement, PLoS Med, 2009, Vol. 6, page no. e1000097, doi:10.1371/journal.pmed1000097 © PRISMA Statement or PRISMA Explanation and Elaboration. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Structure of the outcomes of the reviews on benefits and harms of mammography, ultrasonography, clinical breast examination and breast self‐examination. *Final outcomes for the benefits of screening: breast cancer mortality, all‐cancer mortality, all‐cause mortality; final outcomes for harms of screening: overdiagnosis, overtreatment, false ‐positive diagnosis, and radiation ‐induced deaths. **Intermediary outcomes for the benefits of screening: sensitivity, size and proportion of small and advanced of tumours at diagnosis, proportional interval cancer rate, interval cancer ratio, positive predictive value; Intermediary outcomes for the harms of screening: specificity, recall rates. Abbreviations: FM, field mammography; DM, digital mammography.

Figure 3

Breast cancer mortality reduction among (a) all age groups, (b) 50–69 year‐old, (c) <50 year‐old, (d) >69 year‐old women. Duke group (2014): (1) Case–control studies, (2) Incidence – based mortality studies; Gotzsche (2013): (1) All randomised trials; (2) Truly randomised trials; Canadian task force (2011): (1) All randomised trials; (2) Truly randomised trials; Irvin (2014): (1) Birth cohort comparison; (2) Geographical comparison; (3) Geographical‐Historical Comparisons. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Overdiagnosis rate reported in systematic reviews of (a) randomised controlled trials and (b) observational studies. Dashed line: a—Low risk of bias studies, b—Models. Source of cases in denominators: Hamashima, 2016 [20] ‐ not described; Biesheuvel, 2007 [47]—unscreened; Carter, 2015 – mixed (unscreened – 10%, screen expected – 4‐76%, screen detected – 17‐ 31%); Chen, 2017 ‐ unscreened; Duke Synthesis Group, 2014 [9] – not described (unscreened −29%, screen detected −19%, entire follow up – 11%); The UK Panel, 2012 [6] – screen detected (16–19%) and entire follow up (10–11%); Myers, 2015 [11] ‐ mixed (screen detected – 19%, entire follow up – 11%); Nelson, 2016 [12] – not described; Canadian Task Force, 2011 [16] ‐ not described; Lee, 2015 [19] ‐ not described. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

False positive cumulative rates with biennial (a) and annual (b) screening. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

Quality of systematic reviews reporting benefits and/or harms of breast cancer screening.