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Published on: September 12, 2019
Effects of screening and systemic adjuvant therapy on ER-specific US breast cancer mortality
Diego Munoz1, Aimee M Near1, Nicolien T van Ravesteyn1
1Division of Biomedical Informatics Research (DM) and Department of Radiology (DM, SKP), School of Medicine, Stanford University, Stanford, CA (DM); Department of Oncology, Georgetown University Medical Center and Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC (AMN, YC, JSM); Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (NTvR, HJdK, EAMH); Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School Boston, MA (SJL, HH); Departments of Family and Social Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (CBS); Department of Industrial and Systems Engineering, University of Wisconsin, Madison, WI (OA, MAE); Carbone Cancer Center, University of Wisconsin, Madison, WI (ESB, ATD); University of Texas M.D. Anderson Cancer Center, Houston, TX (DAB, GC); Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA (NKS); Department of Surgery, College of Medicine, University of Vermont, VT (BLS).
Background:
Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker.
Methods:
We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy.
Results:
In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13-21) and 5 per 100000 women (model range = 3-6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%-87.8% vs 85.7%-96.5%).
Conclusion:
As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms.
