From pathogenesis to hormone prevention of mammary carcinogenesis.

The study of an experimental model, the induction of breast carcinomas by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) to virgin rats, has allowed us to determine that the susceptibility of the mammary gland to a carcinogen depends upon its degree of differentiation at the time of exposure. The mostly undifferentiated gland of young virgin rats is highly susceptible due to the high proliferative rate of the terminal ductal structures or terminal end buds (TEBs), ready for differentiation into alveolar buds (ABs) which avidly bind the carcinogen. Complete differentiation through a full-term pregnancy renders the gland resistant to carcinogenesis due to the replacement of TEBs by lobules whose epithelium has a low proliferative rate and low DMBA binding. Although pregnancy is the most complete stimulus, differentiating the highly susceptible TEBs of the virgin female into more resistant lobules, administration of certain pituitary, ovarian or placental hormones considerably modifies the mammary gland structure, thus influencing its response to chemical carcinogenesis. The observation that contraceptive agents administered for a short period of time also exert a protective effect allows us to postulate that this model could be developed as a protocol for breast cancer prevention.