Effects of Hormone Replacement Therapies and Dietary Phytoestrogens on the Mammary Gland of Macaques

摘要

The purpose of this study has been to use histomorphometric and immunohistochemical techniques to study the incidence and characteristics of mammary gland hyperplasia, dysplasia and other possible indicators of breast cancer risk, in cynomolgus macaques given long-term hormonal treatments. Treatments evaluated to date include conjugated estrogens (CEE), medroxyprogesterone acetate (MPA), the combination of CEE and MPA, tamoxifen, estradiol (E2), 17alpha-dihydroequilenin (DHEN), soybean phytoestrogens (SBE), and SBE + E2. Pathologic evaluation, histomorphometric evaluations, and staining for estrogen receptor, progesterone receptor, and the proliferation marker Ki-67 MIB were done. Results are as follows: The addition of MPA to CEE therapy increases, rather than decreases, mammary gland proliferation. Tamoxifen treatment does not induce mammary gland proliferation beyond that seen in controls; this is in contrast to a marked uterotrophic effect. DHEN does not induce mammary gland or endometrial proliferation. Soybean estrogens do not induce mammary or endometrial proliferation when given alone, and exert an antagonistic effect on E2-induced proliferation. New work includes dietary modulation of hormonal effects on mammary gland, interactions of tamoxifen and estradiol, identification of p53expression in CEE-treated macaque mammary gland, assessment of expression of estrogen receptor beta, and further agonist/ antagonist effects of soy phytoestrogens.