EFFECTS OF CONJUGATED ESTROGENS, MEDROXYPROGESTERONE ACETATE, AND TAMOXIFEN ON THE MAMMARY-GLANDS OF MACAQUES

The purpose of this work was to examine the mammary glands of adult, o variectomized female cynomolgus macaques (Macaca fascicularis) in a lo ng-term study or: the effects of hormone treatments on chronic disease . Treatments included conjugated equine estrogens (CEE), medroxyproges terone acetate (MPA), CEE+MPA, and tamoxifen. Doses were scaled from t hose given women. Treatments were given in the diet for three years, f ollowed by necropsy and tissue collection. Endpoints evaluated include d glandular histology, histo morphometry, and immunohistochemical dete ction of the proliferation marker Ki-67, estrogen receptor (ER), and p rogesterone receptor (PR) in mammary epithelial cells. Major findings were as follows: CEE induced PR expression and focal to diffuse lobulo alveolar proliferation. Proliferation was increased by the addition of MPA, but was not induced by MPA alone. Tamoxifen induced ER and PR bu t not Ki-67 expression or glandular hyperplasia. Neoplasms were not se en. These findings indicate that progestogens may exacerbate, not anta gonize mammary gland proliferation induced by estrogen replacement the rapy, and that tamoxifen has both estrogen agonist and antagonist effe cts on sex steroid receptor expression in the normal primate breast.