The effect of treatment advances on the mortality results of breast cancer screening trials: A microsimulation model

Background: Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. Objective: To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Design: Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but re-flecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Data Sources: Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. Target Population: U.S. women aged 50 to 74 years. Time Horizon: 10 and 25 years. Perspective: Population. Intervention: Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Outcome Measures: Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. Results of Base-Case Analysis: At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10 000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10 000 women. Results of Sensitivity Analysis: Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Limitation: Disease models simplify reality and cannot capture all breast cancer subtypes. Conclusion: Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. Primary Funding Source: University of Washington and National Cancer Institute.