Risk reduction or prophylaxis of breast cancer with tamoxifen is a controversial intervention. The decision to take or recommend tamoxifen presents a range of potential outcomes and associated costs which must be considered in both individual and clinical policy decisions. Objectives: The primary objectives of this 3 year proposal are: (1) to evaluate women's acceptance and utilities for the outcomes of tamoxifen prophylaxis of breast cancer, (2) to evaluate the association of self-perceived breast cancer risk with preferences for tamoxifen prophylaxis compared to the association of calculated breast cancer risk using the NCI Gail breast cancer risk screening tool with preferences for tamoxifen prophylaxis and (3) to determine the marginal cost- effectiveness of tamoxifen prophylaxis for reduction of breast cancer mortality compared with annual screening by clinical breast exam and mammography. Methods: We will collect cross- sectional data from interviews with 300 women as well as perform secondary analyses on pre-existing data. Utilities and patient preferences will be collected from interviews with 300 women potentially eligible for tamoxifen prophylaxis, as identified through use of the NCI Gail breast cancer risk screening tool. Because low income minority women have been largely excluded from clinical trials examining tamoxifen prophylaxis, particular efforts will be made to recruit African American and Latina women participating in California's Breast Cancer Early Detection Program for assessment of these parameters. Costs will be derived from Medicare average allowed charges and average wholesale prices for outpatient medications. Model probabilities will be determined when possible from a systematic review of the literature, relying primarily on recent published results from randomized trials and a large meta-analysis for relative risks of tamoxifen related outcomes, and population based data or large cohort studies for estimating baseline risks. When probabilities are not available from the medical literature, expert opinion will be solicited from a panel using a modified Delphi process. Outcomes will include breast cancer, endometrial cancer, venous thromboembolism, stroke, hip fracture, cataracts, and bothersome side effects. The cost-effectiveness analysis will be based on modifications of a previously developed Markov process model. One way and two way, sensitivity analyses and Monte Carlo analysis will be conducted. Expected results: Findings from this project will enhance understanding of women's decisionmaking about tamoxifen prophylaxis, identify key parameters influencing cost effectiveness of tamoxifen prophylaxis, and provide perspective on the marginal cost effectiveness of tamoxifen compared with other preventive interventions, outside the context of randomized controlled trials.