Epidemiological evidence, as well as experimental studies, reveal that early parity protects the mammary gland from the risk of subsequent carcinoma development, whereas nulliparity, late first full-term pregnancy and abortion are associated with a greater risk. The study of an experimental model, the induction of breast carcinomas by administration of the chemical carcinogen 7, 12-dimenthylbenz(a)anthracene (DMBA) to virgin rats, has allowed us to determine that the susceptibility of the mammary gland to the carcinogen depends upon the degree of differentiation of the gland. 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 in alveolar buds (ABs) which avidly bind the carcinogen. Full differentiation through a full-term pregnancy renders the gland refractory to carcinogenesis, due to the replacement of TEBs by lobules whose epithelium has a low proliferative rate and low DMBA binding. Since this protective effect is mediated by ovarian and placental hormones, it is of practical interest to determine whether this pregnancy-mediated protection can be induced in young virgin rats by means of exogenous hormonal stimulation mimicking gestation, but without the need of a full term pregnancy. We postulate that this degree of differentiation can be achieved by administration of contraceptive agents, which are known to stimulate mammary growth. Since the degree of differentiation is critical in the prevention of breast cancer, we propose to determine (1) whether an optimal degree of differentiation can be achieved by administration of progestagens (2) WHETHER THIS ADMINISTRATION INDUCES CHANGES IN THE PITUITARY-ADRENO-OVARIAN AXIS (3) whether there is an optimal age for inducing gland differentiation beyond which the gland becomes refractory to normal development, and (4) whether events such as pregnancy interruption or carcinogen administration prior to hormonal stimulation alter the ability of the gland to undergo full differentiation.
| Russo, J; Russo, I H (1991) Mammary tumorigenesis. Prog Exp Tumor Res 33:175-91 |
| Russo, J; Gusterson, B A; Rogers, A E et al. (1990) Comparative study of human and rat mammary tumorigenesis. Lab Invest 62:244-78 |
| Russo, I H; Gimotty, P; Dupuis, M et al. (1989) Effect of medroxyprogesterone acetate on the response of the rat mammary gland to carcinogenesis. Br J Cancer 59:210-6 |
| Russo, I H; Russo, J (1988) Hormone prevention of mammary carcinogenesis: a new approach in anticancer research. Anticancer Res 8:1247-64 |
| Russo, J; Russo, I H (1987) Biological and molecular bases of mammary carcinogenesis. Lab Invest 57:112-37 |
| Russo, I H; Russo, J (1986) From pathogenesis to hormone prevention of mammary carcinogenesis. Cancer Surv 5:649-70 |
