Chapter 40 - Hormone Replacement Therapy and Breast Cancer

Abstract

There is compelling evidence that ovarian hormones, e.g., estrogen and possibly progesterone, have a principal role in the development of breast cancer. There is a 100-fold difference in incidence between women and men, and premenopausal oophorectomy is clearly protective. Further, the changes in incidence with age differ from the steady increase seen for non-hormone-dependent cancers. Breast cancer incidence increases rapidly with age up to age 50 years, which is roughly the mean age at natural menopause and consequently the time of cessation of ovarian estrogen and progesterone production. Estrogens are known to stimulate proliferation of thebreast epithelium, and a quantitative review of prospective data concluded that risk of breast cancer was significantly increased among women with higher serum levels of estradiol. Progesterone was formerly thought to antagonize the proliferatory effect of estrogen and thereby reduce breast cancer risk. Results from in vitro studies—in which cells are separated from the complex hormonal milieu of breast tissue in vivo—do suggest that progestins can antagonize estrogen-stimulated growth of human breast cells.