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Original Investigation
January 9, 2018

Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012

Author Affiliations
  • 1Departments of Radiology and Biomedical Data Science, School of Medicine, Stanford University, Stanford, California
  • 2Departments of Medicine and Health Research and Policy, School of Medicine, Stanford University, Stanford, California
  • 3Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
  • 4Department of Industrial and Systems Engineering, University of Wisconsin-Madison
  • 5Carbone Cancer Center, University of Wisconsin-Madison
  • 6Department of Oncology, Georgetown University Medical Center and Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC
  • 7Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
  • 8Department of Public Health, Erasmus MC University Medical Center, Rotterdam, the Netherlands
  • 9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston
  • 10Departments of Family and Social Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
  • 11Department of Surgery, College of Medicine, University of Vermont, Burlington
  • 12Department of Biostatistics and Medical Informatics and Population Health Sciences, University of Wisconsin-Madison School of Medicine and Public Health
JAMA. 2018;319(2):154-164. doi:10.1001/jama.2017.19130
Key Points

Question  What are the associations of screening and adjuvant treatment with reductions in US breast cancer mortality rates by molecular subtype?

Findings  In this study of 6 simulation models that projected US breast cancer mortality trends for women aged 30 to 79 years, advances in treatment, such as use of newer adjuvant therapies, compared with screening advances were associated with greater estimated reductions in overall breast cancer mortality from 2000 to 2012, although the associations varied by breast cancer molecular subtype.

Meaning  Simulation modeling estimated that advances in treatment were associated with greater decreases in breast cancer mortality rates than advances in screening, although these associations varied by molecular subtype.

Abstract

Importance  Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden.

Objective  To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu).

Design, Setting, and Participants  Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated.

Exposures  Screening mammography and treatment.

Main Outcomes and Measures  The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment.

Results  In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1%-6%) with trastuzumab. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER+/ERBB2−, 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+/ERBB2+, 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER−/ERBB2+, 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER−/ERBB2−, 48% (model range, 38%-57%) vs 52% (model range, 44%-62%).

Conclusions and Relevance  In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype.

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