Experimental basis for the prevention of breast cancer.

Cancer chemoprevention involves intervention in the carcinogenic process by a natural or synthetic chemical that either blocks neoplasia development or arrests malignant phenotype progression. The chemopreventive test agent must experimentally be established as safe before a clinical trial. In our laboratory, inhibition of carcinogen-induced development of precancerous lesions in the mouse mammary gland organ culture model is used as a primary screen to select chemopreventive agents for in vivo efficacy evaluation. A nearly 75% correlation apparently exists between the efficacy observed in vitro and in vivo carcinogenesis. For in vivo experiments, MNU- and DMBA-induced mammary tumours in rats are the models of choice. Numerous agents have been identified and progressed to preclinical toxicity and clinical trials. More recently, combination chemoprevention has received considerable attention, since no known chemopreventive agent sufficiently reduces tumour incidence in rats. The sequence of events for establishing the experimental basis for chemoprevention of breast cancer is described.