Breast cancer remains the leading cause of cancer morbidity and mortality among American women aged 15 to 74 years. Thus, in addition to traditional modalities for cancer therapy, new strategies for breast cancer prevention are needed in the attempt to control the disease. In order to define pharmacologic regimens with increased efficacy in the prevention of breast cancer, studies are proposed which will provide quantitative data concerning interactions among inhibitors of chemical carcinogenesis in the rat mammary gland. In the preliminary series of studies, retinyl acetate, butylated hydroxyanisole, indomethacin, or dehydroepiandrosterone will be administered for defined periods with respect to administration of the mammary gland carcinogens 7,12-dimethylbenz(a)anthracene or N-methyl-N-nitrosourea. Inhibition of carcinogenesis will be defined as a reduction in cancer incidence, decreased carcinoma multiplicity, or increased cancer latent period. On the basis of data generated in these studies, a second series of experiments will be conducted in which combinations of modifiers found to be active in mammary cancer chemoprevention will be administered in the attempt to increase the efficacy of cancer inhibition achieved with any single agent alone. In this manner, combinations of agents with enhanced chemopreventive activity will be identified, and the synergistic, additive, or non-additive inhibition achieved by various combinations of modifiers will provide information concerning possible mechanism(s) of action.