title: The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.
abstract: 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.
  
  
  METHODS
  Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status).
  
  
  METHODS
  Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry.
  
  
  METHODS
  U.S. women aged 50 to 74 years.
  
  
  METHODS
  10 and 25 years.
  
  
  CONCLUSIONS
  Population.
  
  
  METHODS
  Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab.
  
  
  METHODS
  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
  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
  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%.
  
  
  CONCLUSIONS
  Disease models simplify reality and cannot capture all breast cancer subtypes.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  University of Washington and National Cancer Institute.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Birnbaum
authors.forename: Vijayakrishna K
authors.initials: VK
authors.lastname: Gadi
authors.forename: Elan
authors.initials: E
authors.lastname: Markowitz
authors.forename: Ruth
authors.initials: R
authors.lastname: Etzioni
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D003198:Computer Simulation; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008327:Mammography; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents