Long term absence of invasive breast cancer diagnosis in 2,402,672 pre and postmenopausal women: A systematic review and meta-analysis

Background: Invasive Breast Cancer (IBC) risk estimates continue to be based on data collated from cancer registries, i.e., retrospective research that excludes disease-free women. For women without a prior diagnosis, these estimates inflate both risk and screening frequency recommendations and inadvertently increase recently recognized harms from overdiagnosis and overtreatment. Objective: To estimate the likelihood that pre or postmenopausal women with no prior diagnosis will remain free of IBC in order to enable evidence-based screening recommendations. Methods: Prospective data from 21 studies of 2,402,672 women were analyzed, updating our previously published systematic search of 19 studies. This second systematic search included PubMed and The Cochrane Library from 2012 through April 2019. Inclusion criteria: only studies reporting the number of women enrolled, length of follow-up, and number of women diagnosed with IBC. Linear regression was used to estimate the percentage of women expected to remain free from an IBC diagnosis based on follow-up duration. To minimize non-response bias and selective outcome bias, only studies reporting outcomes for all enrolled women followed for similar, specific lengths of time were included. Sensitivity analyses confirm that the overall findings were unchanged by age at enrollment, menopausal status, screened women, variation in sample size, duration of follow-up, and heteroskedasticity. Results: The calculated percentage of women remaining IBC-free after follow-ups of 5, 10, 15, 20 and 25 years decreases uniformly by about one-fourth of one percent per year, i.e., 0.255% (95% CI: -0.29, -0.22; p