In Southeast Asian populations, a high-soy diet has been associated with a low incidence of breast cancer. A soy diet also has suppressed chemically induced mammary tumors in animal models. Isoflavones may protect against mammary tumors by promoting early differentiation. Phytoestrogens in soy are partial estrogen agonists or antagonists and seem to inhibit the proliferation of breast cancer cells in vitro. This study examined the effects of taking a dietary soy supplement of 60 gm (45 mg of isoflavones) on the normal breasts of 84 premenopausal women with breast symptoms who were attending a clinic. Final results were available for 28 women taking soy protein in addition to a normal diet and 23 control women. Twenty of the study patients completed 13 to 14 days of supplementation. Nipple aspirates were analyzed for apolipoprotein D and pS2, both of which are estrogen regulated and are used as markers of estrogen action on the breast. A small sample of grossly normal breast tissue was taken at least 1 cm from the lesion site.
Levels of the phytoestrogens genistein and daidzein in nipple aspirates were higher than in paired serum specimens before and after soy supplementation, but no significant increase in isoflavone levels was noted in response to soy supplementation. Levels of apolipoprotein D in nipple aspirates were significantly reduced after soy supplementation, whereas levels of pS2 were elevated. Supplementation had no apparent effect on the proliferation of breast epithelial cells, estrogen or progesterone receptor status, apoptosis, mitosis, or the expression of Bcl-2. This was the case even after adjusting for age, menstrual cycle, parity, and oral contraceptive use. Although short-term dietary soy supplementation does exert a weak estrogenic action on the premenopausal breast, no antiestrogenic effect was noted in this study. The estrogenic response may be too little to elicit a proliferative epithelial response.
J Clin Endocrinol Metab 1999;84:4017–4024