Public Health Mode Personalized Medicine: Risk Stratification for Breast Cancer Screening

Background: Breast cancer (BC) screening, primarily age-based, is a major public health program in many wealthy countries. At the same time, there is a dramatic increase in using genetics to support personalized medicine. These two approaches would seem antithetical. However, they can join powerfully with the possibility of using genetic information as the basis for a major shift from age-based to a risk-based BC screening programs. Aim: To assess the prospective cost-effectiveness of such a shift to risk-based BC screening requires representative population data on the relationships among a woman's age when a risk assessment is done, her family history of cancer in the context of pedigree data, and specific features of her genotype - comprising both the presence of rare genetic mutations like BRCA1/2 and recently derived polygenic risk scores. We use our newly developed Genetic Mixing Model (GMM) to estimate this joint distribution as the initial step in assessing the prospective cost-effectiveness of ri...