(CIT): We have known for over 300 years that reproductive factors in women impact their subsequent risk of breast cancer. We have had good evidence that the ovary is likely to play a central role in breast cancer risk and natural history for over 100 years. We have known from the laboratory about the carcinogenicity of estrogen for almost 70 years. In addition, over the last 50 years, epidemiologists have identified over 20 independent risk factors for breast cancer, with all but a few having obvious hormonal implications. Over this same period of time, laboratory research on hormonal carcinogenesis has gained progressively more sophisticated insights into the mechanisms of action of hormones in physiologic and pathologic processes within the breast. As a result of all of this, a number of hypotheses have been developed to explain the hormonal etiology of breast cancer. Some of these have focused on mechanistic explanations of a single risk factor, while others have focused on unifying hypotheses designed to provide mechanisms that would explain many recognized risk factors. A number of these hypotheses have become widely accepted, with a few perceived as having moved from hypotheses to established facts, prompting the development of candidate interventions to prevent breast cancer. The purpose of this presentation will be to review what we know about hormonally-related breast cancer risk factors in human populations and some of the prominent hypotheses to explain them, and to then critically review how what we currently know supports or doesn't support these hypotheses. The overall goal will be to determine what we know well enough about breast hormonal carcinogenesis to proceed to practical prevention measures, and where a priority focus on research (laboratory and population) would be needed. Dr. Hoover is a physician-epidemiologist who is currently the Director of the Epidemiology and Biostatistics Program in the Intramural Research Program o...