1. CISNET and BCSC: Working Together To Model The Population Impact Breast Cancer Screening A Celebration of the Work of the Breast Cancer Surveillance Consortium April 27, 2010 Kathleen Cronin Surveillance Research Program National Cancer Institute

2. Cancer Intervention and Surveillance Modeling Network (CISNET)  NCI Sponsored Consortium of Modelers Focused on Modeling of the Impact of Cancer Control Interventions on Current and Future Population Trends in Incidence and Mortality Optimal Cancer Control Planning  15 funded grantees in Breast, Prostate, Colorectal, and Lung Cancer  Comparative modeling approach Base Cases - joint modeling exercises with common inputs Model Profiler - series of templates for describing models

3. Breast Cancer Investigators in CISNET Dana Farber - Marvin Zelen, Sandra Lee Erasmus University – Dik Habbema, Harry de Koning Georgetown University – Jeanne Mandelblatt MD Anderson – Donald Berry Stanford University – Sylvia Plevritis University of Rochester – Andrei Yakovlev University of Wisconsin – Dennis Fryback NCI – Rocky Feuer, Kathy Cronin

4. General Formulation of CISNET Models Risk Factors Screening Behavior Diffusion of New Treatments Cancer Models Example Outputs: Mortality Incidence Quality–Adjusted Life Years Overdiagnosis Medical costs Common Inputs Simulation or Analytical Model Common Outputs: Benefits and Harms of Interventions

5. Development and Validation of Breast Cancer Natural History Models BCSC data played a key role in the development and validation of the central cancer models that represent the natural history of disease  Characteristics of cases conditioned on the time since last screening test  Characteristics of screen detected cases Stage distribution ER status  Age dependent sensitivity and specificity of mammography False positive rates Unnecessary biopsies

6. Modeling the Dissemination and Usage of Mammography in the US Population BCSC provided data on repeat mammography use and collaborated with CISNET to develop a model to describe the patterns of mammography use in the population  Classified women who ever have a mammogram into categories of screeners Annual Biennial Irregular  Use longitudinal data on individual women to estimate the time between successive screening exams for each category

7. Distribution of Screening Categories By Age

8. Time Between Subsequent Screening Exams For Women age 50-59 Annual Biennial Irregular

9. Modeled Mammography Screening Over Time, Women age 40-79 Biennial

10. Application: Modeling the Impact of Screening and Adjuvant Treatment On Breast Cancer Mortality Observed US Mortality No Screening or Adjuvant Treatment Screening only Treatment Only Both Screening and Treatment

11. Estimated Percent Decline in Mortality Due To Screening and Adjuvant Therapy For The 7 Models Berry et al. N Engl J Med 2005: Seven statistical models showed that both screening mammography and treatment have helped reduce the rates of death from breast cancer

12. Application: Modeling the Harms and Benefits of Different Screening Schedules  Analysis requested by the USPSTF  Two primary measures of benefit (vs. no screening): % reduction in breast cancer mortality Life years gained (per 1000 women)  Exposure to harms: False positive screens Number of un-necessary biopsies Detection of tumors never destined to cause breast cancer death (“over diagnosis”)

13. Breast Cancer Screening Strategies Annual Biennial #Strategy 0No Screening 140-69 240-79 340-84 445-69 550-69 650-74 750-79 850-84 955-69 1060-69

14. D G S M E W B60-69 B50-84 A40-84 B60-69 B50-79 B40-84 A40-84 B60-69 B50-79 A40-84 B50-84 B60-69 B50-69 A40-84 B40-84 B60-69 B50-74 B40-84 A40-84 B50-84 B60-69 B55-69 B50-84 A40-84 B50-74 B40-84 B55-69 B40-84 B55-69 B50-84 B55-69 B50-69 B50-79 B50-69 B50-74 B50-79 B50-74 B50-69 B55-69 B50-69 B50-74 B40-84 B55-69 B50- 74 B50-84 B50-79 B50-69 Efficiency frontier for each model Each dot is a strategy (Red dot is annual screening ages 40-79) All models reached qualitatively similar results Moving from annual to biennial maintains on average 81% of the benefits with reduced harms

15. Looking Ahead  BCSC continues to be a primary resource for the CISNET consortium on many levels Population level data on screening usage and outcomes not available elsewhere Provide expertise on use and interpretation of data Active collaborator on a number of research questions  Next Steps Activities to Promote Research Collaborations (APRC) – CISNET/BCSC/EPC Compare effectiveness of film vs. digital in subgroups of women Grand Opportunities (GO) Grant Compare clinical and cost-effectiveness of various screening strategies