Soy Isoflavone Supplementation and Mammographic Density in Postmenopausal Women

描述(由申请人提供)：在美国，每年每10万名妇女中有26人死于乳腺癌，发病率的上升在所有年龄段的妇女中都是一个严重的问题。大豆食品含有高浓度的异黄酮类，可能会预防乳腺癌，但人们对异黄酮类预防乳腺癌的潜在益处以及对高危女性使用异黄酮类药物的安全性尚不清楚。乳房X光摄影密度已被证明是乳腺癌风险的一个很好的标志。激素替代疗法，特别是黄体酮，会增加乳房密度，而他莫昔芬治疗会降低乳房密度。拟议项目的目标是使用从406名绝经后妇女收集的乳房X光照片来确定异黄酮补充剂和乳房X光检查密度之间的关系。这些妇女参加了一项为期两年的多地点、随机、双盲和安慰剂对照研究，即使用大豆预防骨质疏松症(OPUS)研究。在OPUS研究中，这些妇女被随机安排，三分之一的妇女每天服用80毫克的苷元大豆异黄酮，三分之一的妇女每天服用120毫克的苷元大豆异黄酮，其余三分之一的妇女服用安慰剂，疗程为2年。分别在治疗前、治疗12个月和24个月后进行钼靶筛查，并用灵敏的四重质谱仪测定异黄酮类及其代谢物的血药浓度。在夏威夷癌症研究中心使用柯达LS85胶片数字化仪扫描乳房X光照片后，将使用计算机辅助定量方法评估乳房密度。读者将对受试者的分组分配和乳房X光检查的时间顺序视而不见。随机抽取的胶片样本将一式两份读取，以进行质量控制。统计分析将应用一般线性模型来比较不同治疗组的乳房X线片测量结果，同时考虑重复测量。该项目将基于从最大规模的异黄酮类暴露研究中收集的数据，提供关键信息，以证明绝经后妇女服用异黄酮类补充剂与乳房X光照相密度之间的关系。随着美国大豆消费量创历史新高，拟议中的项目将为公众提供急需的关于大豆异黄酮补充剂预防乳腺癌安全性的科学数据。

DESCRIPTION (provided by applicant): Breast cancer accounts for 26 annual deaths per 100,000 women in the United States and the rising incidence is a serious concern among women of all ages. Soy foods, which contain high concentrations of isoflavones, might protect against breast cancer, but the potential preventive benefit of isoflavones against breast cancer and the safety of administering isoflavones to high-risk women are not well understood. Mammographic density has been shown to be an excellent marker for breast cancer risk. Hormone replacement therapy, in particular progesterone, increases breast densities, whereas tamoxifen therapy decreases densities. The goal of the proposed project is to determine the relationship between isoflavone supplementation and mammographic densities using the mammograms collected from 406 postmenopausal women who participated in a 2-year multi-site, randomized, double-blind, and placebo-controlled study, the Osteoporosis Prevention Using Soy (OPUS) study. In the OPUS study, the women were randomized so that 1/3 of the women receive 80 mg/d of aglycone soy isoflavones, 1/3 receive 120 mg/d of aglycone soy isoflavones, and the remaining 1/3 receive a placebo for 2 years. Screening mammograms and blood concentrations of isoflavones and their metabolites measured by sensitive quadruple mass spectrometry were obtained at baseline and after 12 and 24 months of treatment. After scanning the mammograms films at the Cancer Research Center of Hawaii using a Kodak LS85 Film Digitizer, breast density will be assessed using a computer-assisted quantitative method. The reader will be blinded to the group assignment of the subjects and the time sequence of the mammograms. A random sample of films will be read in duplicate for quality control. The statistical analysis will apply general linear models to compare mammographic measures by treatment group, while considering the repeated measures. The project will provide critical information, based on data collected from the largest follow-up study with the highest isoflavone exposure, to document the relation between isoflavone supplementation and mammographic density in postmenopausal women. With the consumption of soy at record high in the United States, the proposed project will provide the much needed scientific data to the public on the safety of soy isoflavone supplementation against breast cancer.