McMichael-Phillips D F, Harding C, Morton M, Roberts S A, Howell A, Potten C S, Bundred N J
Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.
Am J Clin Nutr. 1998 Dec;68(6 Suppl):1431S-1435S. doi: 10.1093/ajcn/68.6.1431S.
A high dietary intake of soy products (eg, as in Japan and Singapore) has been associated with a reduction in the incidence of breast cancer in premenopausal women. Phytoestrogens present in soybeans inhibit human breast cancer cell proliferation in vitro and breast cancer development in animal models, but no data exist on the effects of phytoestrogens on histologically normal human breasts. This study examines the effects of dietary soy supplementation on the proliferation rate of premenopausal, histologically normal breast 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 45 mg isoflavones) taken daily for 14 d. Biopsy samples of normal breasts were labeled with [3H]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 were measured in serum samples obtained before and after supplementation. Serum concentrations of the isoflavones genistein and daidzein increased in the soy group at 14 d. Results showed a strong correlation between Ki67 and the thymidine labeling index (r = 0.868, P < or = 0.001). The proliferation rate of breast lobular epithelium significantly increased after 14 d of soy supplementation when both the day of menstrual cycle and the age of patient were accounted for. Progesterone receptor expression increased significantly in the soy group. Short-term dietary soy stimulates breast proliferation; further studies are required to determine whether this is due to estrogen agonist activity and to examine the long-term effects of soy supplementation on the pituitary gland and breast.
高膳食摄入大豆制品（如在日本和新加坡）与绝经前女性乳腺癌发病率降低有关。大豆中含有的植物雌激素在体外可抑制人乳腺癌细胞增殖，并在动物模型中抑制乳腺癌发展，但尚无关于植物雌激素对组织学正常的人类乳腺影响的数据。本研究考察了膳食补充大豆对绝经前组织学正常乳腺上皮细胞增殖率及孕激素受体表达的影响。患有良性或恶性乳腺疾病的女性（n = 48）被随机分配，一组仅接受正常饮食，另一组在14天内每天额外摄入60克大豆补充剂（含45毫克异黄酮）。正常乳腺的活检样本用[3H]胸腺嘧啶核苷标记以检测处于S期的细胞数量，并进行免疫细胞化学染色以检测增殖抗原Ki67。在补充前后采集血清样本，测定其中的植物雌激素染料木黄酮、大豆苷元、雌马酚、肠内酯和肠二醇。大豆组在14天时血清中染料木黄酮和大豆苷元这两种异黄酮的浓度升高。结果显示Ki67与胸腺嘧啶核苷标记指数之间存在强相关性（r = 0.868，P≤0.001）。在考虑月经周期天数和患者年龄的情况下，补充大豆14天后乳腺小叶上皮细胞的增殖率显著增加。大豆组中孕激素受体表达显著增加。短期膳食大豆刺激乳腺增殖；需要进一步研究以确定这是否归因于雌激素激动剂活性，并考察大豆补充剂对垂体和乳腺的长期影响。
