Differentiation and breast cancer.

The mammary gland is an organ whose size, shape and function undergo fundamental changes during the various phases of a woman's growth. Although the development of the mammary gland begins during infancy, the most dramatic changes occur with the initiation of puberty. Pregnancy and lactation complete the functional development of the organ, which regresses during menopause. Epidemiological and experimental studies have demonstrated that certain hormonal influences, especially those related to reproduction, modify the risk of developing breast cancer. Thus, a full term pregnancy completed before the age of 24 years significantly reduces the lifetime incidence of breast cancer. Although the mechanism through which pregnancy protects the breast from breast cancer has not been clearly established, experimental models of mammary carcinogenesis have allowed researchers to determine that pregnancy inhibits 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 ulterior hormonal changes. It is postulated that the same mechanism might be responsible for the protective effect of a woman's early first full term pregnancy. The greater incidence of breast cancer observed in nulliparous women correlates well with the greater susceptibility of the virgin rat to develop mammary carcinomas when exposed to chemical carcinogens. The successful induction of malignant transformation in the virgin animal mammary epithelium is due to the presence of undifferentiated structures with a high rate of cell proliferation. These structures are eliminated by pregnancy. The breast of nulliparous women retains those undifferentiated structures, which increase the predisposition of the organ to undergo malignant transformation, which will manifest itself clinically several years after its initiation. The correlation of human epidemiological, clinical and experimental data with those data obtained in rodent experimental models lends support to this hypothesis.