Breast cancer is the most common non-skin cancer among women in the United States, and continues to be an important cause of morbidity and mortality for women at high risk of developing the disease. The advent of preventive intervention and early detection of cancer brings greater hope to the control of breast cancer, while also posing significant challenges to researchers and public health policy makers. The primary objective of this proposal is to provide quantitative frameworks to describe the natural history of breast cancer; assess the impact of the secondary and primary preventive interventions on the natural progression of the disease; evaluate patterns of screening sensitivity by tumor size at detection; search for optimal screening intervals for women in different age groups and optimal screening strategies based on both medical benefit and adverse risk (or cost); and assess the cost and benefit trade-off for chemoprevention used in combination with early detection programs to control breast cancer. Data from randomized screening trials and randomized clinical trials of chemopreventive agents will be analyzed in proposed studies. Theoretic and simulation-based methods will be explored in developing models, estimations, and inference of the quantities that describe the impact of early detection programs and chemopreventive agents in the control of breast cancer. A comprehensive microsimulation model will be developed to evaluate the costs and benefits of various combinations of prevention and screening strategies in order to determine the best allocation of health care resources in the prevention and treatment of breast cancer.