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. 2018 Jan 9;319(2):154-164.
doi: 10.1001/jama.2017.19130.

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

Sylvia K Plevritis  1 , Diego Munoz  1 , Allison W Kurian  2 , Natasha K Stout  3 , Oguzhan Alagoz  4   5 , Aimee M Near  6 , Sandra J Lee  7 , Jeroen J van den Broek  8 , Xuelin Huang  9 , Clyde B Schechter  10 , Brian L Sprague  11 , Juhee Song  9 , Harry J de Koning  8 , Amy Trentham-Dietz  5 , Nicolien T van Ravesteyn  8 , Ronald Gangnon  5   12 , Young Chandler  6 , Yisheng Li  9 , Cong Xu  1 , Mehmet Ali Ergun  4 , Hui Huang  7 , Donald A Berry  9 , Jeanne S Mandelblatt  6
Affiliations

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

Sylvia K Plevritis et al. JAMA. .

Erratum in

  • Error in Figure.
    [No authors listed] [No authors listed] JAMA. 2018 Feb 20;319(7):724. doi: 10.1001/jama.2018.0632. JAMA. 2018. PMID: 29466570 Free PMC article. No abstract available.

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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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Plevritis reported consulting for GRAIL. Dr Alagoz reported consulting for Renaissance Rx and Ally Clinical Diagnostics. Dr de Koning reported receiving grant funding from the Dutch National Institute for Public Health and the Environment and SCOR Global. Dr Berry reported being the co-owner of Berry Consultants. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Dissemination of Screening Mammography, Type of Mammography, and Adjuvant Therapy Among US Women, 1975-2012
A, Based on data from multiple rounds of the National Health Interview Survey over time and Breast Cancer Surveillance Consortium (BCSC) data from 1994 to 2012. B, Based on Mammography Quality Standards Act of 1992 data on digital mammography facilities from the US Food and Drug Administration and the BCSC. C, An exemplar stage and set of molecular markers (node-positive AJCC 6 stage 2b, ER+/ERBB2−) at diagnosis based on data from Surveillance, Epidemiology, and End Results (SEER) special patterns of care studies and the National Comprehensive Cancer Network. These data were used for all other combinations of ages, stages, and molecular subtypes. In general, starting in the mid-1990s anthracycline-based, multiagent chemotherapy regimens were in use, and, in 1997, taxanes could be added to those regimens. Hormonal therapy began with tamoxifen in the 1980s and, starting in 1997, also included aromatase inhibitors. For women diagnosed with ERBB2+ tumors (not shown in this example), trastuzumab was disseminated independently of other treatments and, based on its immediate rapid uptake, all ERBB2+ patients were modeled as receiving trastuzumab beginning in year 2006. Models used 2010 treatment dissemination data for subsequent years (indicated by the dashed lines).
Figure 2.
Figure 2.. Age-Adjusted Predicted Breast Cancer Mortality Rate Among US Women Aged 30 to 79 Years From 1975-2012
SEER indicates Surveillance, Epidemiology, and End Results. For model abbreviations, see Methods.
See this image and copyright information in PMC

Comment in

References

    1. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Breast Cancer Statistics. https://seer.cancer.gov/statfacts/html/breast.html. Accessed March 31, 2017.
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