Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast

A high dietary intake of soy products (eg, as in Japan and Singapore) has b een associated with a reduction in the incidence of breast cancer in premen opausal women. Phytoestrogens present in soybeans inhibit human breast canc er cell proliferation in vitro and breast cancer development in animal mode ls, but no data exist on the effects of phytoestrogens on histologically no rmal human breasts. This study examines the effects of dietary soy suppleme ntation on the proliferation rate of premenopausal, histologically normal b reast epithelium and the expression of progesterone receptor. Women (n = 48 ) with benign or malignant breast disease were randomly assigned to receive their normal diet either alone or with a 60-g soy supplement (containing 4 5 mg isoflavones) taken daily for 14 d. Biopsy samples of normal breasts we re labeled with [H-3]thymidine to detect the number of cells in S phase and were immunocytochemically stained for the proliferation antigen Ki67. The phytoestrogens genistein, daidzein, equol, enterolactone, and enterodiol we re measured in serum samples obtained before and after supplementation. Ser um concentrations of the isoflavones genistein and daidzein increased in th e soy group at 14 d. Results showed a strong correlation between Ki67 and t he thymidine labeling index (r = 0.868, P less than or equal to 0.001). The proliferation rate of breast lobular epithelium significantly increased af ter 14 d of soy supplementation when both the day of menstrual cycle and th e age of patient were accounted for. Progesterone receptor expression incre ased significantly in the soy group. Short-term dietary soy stimulates brea st proliferation; further studies are required to determine whether this is due to estrogen agonist activity and to examine the long-term effects of s oy supplementation on the pituitary gland and breast.