DIFFERENTIATION AND BREAST-CANCER

The mammary gland is an organ whose size, shape and function undergo f undamental changes during the various phases of a woman's growth. Alth ough the development of the mammary gland begins during infancy, the m ost dramatic changes occur with the initiation of puberty. Pregnancy a nd lactation complete the functional development of the organ, which r egresses during menopause. Epidemiological and experimental studies ha ve demonstrated that certain hormonal influences, especially those rel ated to reproduction, modify the risk of developing breast cancer. Thu s, a full term pregnancy completed before the age of 24 years signific antly reduces the lifetime incidence of breast cancer. Although the me chanism through which pregnancy protects the breast from breast cancer has not been clearly established, experimental models of mammary carc inogenesis have allowed researchers to determine that pregnancy inhibi ts the initiation of the neoplastic process through the induction of a complete differentiation of the mammary gland. This process activates specific genes, which in turn modify the response of the organ to ult erior hormonal changes. It is postulated that the same mechanism might be responsible for the protective effect of a woman's early first ful l term pregnancy. The greater incidence of breast cancer observed in n ulliparous women correlates well with the greater susceptibility of th e virgin rat to develop mammary carcinomas when exposed to chemical ca rcinogens. The successful induction of malignant transformation in the virgin animal mammary epithelium is due to the presence of undifferen tiated structures with a high rate of cell proliferation. These struct ures are eliminated by pregnancy. The breast of nulliparous women reta ins those undifferentiated structures, which increase the predispositi on of the organ to undergo malignant transformation, which will manife st itself clinically several years after its initiation. The correlati on of human epidemiological, clinical and experimental data with those data obtained in rodent experimental models lends support to this hyp othesis.