Common Model Inputs Used in CISNET Collaborative Breast Cancer Modeling

Abstract

Background: Since their inception in 2000, the Cancer Intervention and Surveillance Network (CISNET) breast cancer models have collaborated to use a nationally representative core of common input parameters to represent key components of breast cancer control in each model. Employment of common inputs permits greater ability to compare model output than when each model begins with different input parameters. The use of common inputs also enhances inferences about the results, and provides a range of reasonable results based on variations in model structure, assumptions, and methods of use of the input values. The common input data are updated for each analysis to ensure that they reflect the most current practice and knowledge about breast cancer. The common core of parameters includes population rates of births and deaths; age- and cohort-specific temporal rates of breast cancer incidence in the absence of screening and treatment; effects of risk factors on incidence trends; dissemination of plain film and digital mammography; screening test performance characteristics; stage or size distribution of screen-, interval-, and clinically- detected tumors by age; the joint distribution of ER/HER2 by age and stage; survival in the absence of screening and treatment by stage and molecular subtype; age-, stage-, and molecular subtype-specific therapy; dissemination and effectiveness of therapies over time; and competing non-breast cancer mortality.

Method and results: In this paper, we summarize the methods and results for the common input values presently used in the CISNET breast cancer models, note assumptions made because of unobservable phenomena and/or unavailable data, and highlight plans for the development of future parameters.

Conclusion: These data are intended to enhance the transparency of the breast CISNET models.

Keywords: breast cancer epidemiology; cancer simulation; simulation models.

Figure 1

Age-adjusted overall breast cancer incidence rates per 100,000 women for ages 25 to 84 years. Incidence rates from the age-period-cohort (APC) model estimated with (orange line) and without (blue line) the mammography screening period effect. The green line is observed SEER incidence based on data from nine SEER Registries, 1935–2010. Adapted from Gangnon et al. (23)

Figure 2. Mammography Use of Time

Panel A. The use of screening (annual, every two years, irregular, and never) among women ages 30–79 by calendar year. These observed data were used a targets in modeling dissemination of screening and intervals between screens. Note that the rate of never screened includes women ages 30–39. Panel B. The percent of total mammograms performed in the US that were digital vs. plain film by calendar year. Source: Breast Cancer Surveillance Consortium (BCSC, unpublished data) and the FDA’s Mammography Quality Standards Act and Program. (43)

Figure 2. Mammography Use of Time

Panel A. The use of screening (annual, every two years, irregular, and never) among women ages 30–79 by calendar year. These observed data were used a targets in modeling dissemination of screening and intervals between screens. Note that the rate of never screened includes women ages 30–39. Panel B. The percent of total mammograms performed in the US that were digital vs. plain film by calendar year. Source: Breast Cancer Surveillance Consortium (BCSC, unpublished data) and the FDA’s Mammography Quality Standards Act and Program. (43)

Figure 3

Treatment dissemination. The figure depicts use of adjuvant systemic treatment dissemination from 1975–2010 for an exemplar stage and set of molecular markers (node positive stage IIb, ER+/HER2−) among women 50 to 69 years of age at diagnosis. In the 1980’s and early 1990’s multi-agent chemotherapy (blue line) included primarily CMF regimens; starting in the mid-1990’s antracycline-based regimens were included and increased in use, and in 1998 taxanes could be added to those regimens. Hormonal therapy (red line) began with tamoxifen in the 1980’s and starting in 1997 also included aromatase inhibitors. Hormonal therapy could be used alone or in combination with multi-agent chemotherapy (“both”, green line). Over time, there was an increasing use of both multi-agent chemotherapy and hormonal therapy.

Figure 4

Breast cancer survival curves in the absence of screening and treatment effects stratified by ER and HER2-status, stage and tumor size. These survival curves were shared across all modeling groups.