Mammographic Density and Soy Isoflavones

描述（由申请人提供）：与食用典型西方饮食的人群相比，在许多亚洲国家，食用高水平大豆的人群卵巢激素水平较低，乳腺癌发病率较低，乳房X线摄影密度也较低。我们的临床研究发现，绝经前妇女的卵巢激素水平最低，而她们的饮食提供了15%的能量，来自含有弱雌激素的豆奶。未观察到不良反应。进一步的问题是，雌激素是否是影响乳腺癌风险的关键成分，以及它们是否通过影响乳腺癌的其他可逆风险标志物（如乳腺密度）来实现这一点。乳腺致密的女性患乳腺癌的风险是男性的4-6倍。此外，乳房密度越大，通过乳房X光检查发现早期乳腺癌就越困难。为了验证大豆异黄酮的摄入会降低乳腺密度这一假设，我们提出了一项随机、双盲研究，每组100名绝经前妇女，招募乳腺组织致密性>50%的妇女，随机分配服用大豆异黄酮丸（治疗）或不含大豆异黄酮的安慰剂丸（对照），为期2年。每日剂量为150 mg的总胆甾酮。妇女将在补充干预期间之前和期间提供血液和尿液样本，用于分析卵巢激素和孕酮。在基线和干预期后，将通过乳房X光检查和磁共振成像检查受试者的乳腺密度。通过比较两组在2年干预期间致密乳腺组织的平均变化，并调整基线值和关注的个体患者特征，确定干预的疗效。我们假设，绝经前妇女补充1 - 2年的大豆蛋白将减少内源性雌激素的影响，并进一步降低孕酮水平，这将解释乳腺密度的相应降低。我们的研究结果将对降低乳腺癌风险产生重大影响。降低乳腺密度有望减少乳腺癌发生风险的靶组织体积，并将提高乳腺X线摄影筛查的灵敏度。这项研究可能会导致一种新的，非侵入性和经济的方法来预防乳腺癌。

DESCRIPTION (provided by applicant): Populations consuming high levels of soy, as in many Asian countries, have lower levels of ovarian hormones, lower rates of breast cancer, and reduced mammographic density than populations consuming typical Western diets. These observations may in part be explained by our clinical studies that found ovarian hormone levels of premenopausal women to be lowest while they were consuming a diet that provided 15% energy from soymilk containing weakly estrogenic isoflavones. No adverse effects were observed. Further questions are whether isoflavones are the critical components influencing breast cancer risk and whether they do so by affecting other reversible risk markers for breast cancer, such as breast density. Women with dense breasts have a 4-6 fold excess risk of developing breast cancer. Moreover, greater breast density makes it more difficult to detect early breast cancer by mammography. To test the hypothesis that consumption of soy isoflavones reduces breast density, we propose a randomized, double blind study, with two arms, and 100 premenopausal women in each arm. Women with >50% of dense breast tissue will be recruited and randomly allocated to take soy isoflavone pills (treatment) or placebo pills containing no isoflavones (control) for 2 years. The daily dose will be 150 mg of total isoflavones. Women will provide blood and urine samples before and during the supplement intervention period for the analyses of ovarian hormones and isoflavones. At baseline and after the intervention period, subjects will be examined for breast density by mammography and magnetic resonance imaging. The efficacy of the intervention will be determined by comparing mean changes of dense breast tissue over the 2-year intervention period in the two groups with adjustment for baseline values and individual patient characteristics of interest. We hypothesize that 1 to 2 years of a soy isoflavone supplement in premenopausal women will reduce the effects of endogenous estrogens and reduce progesterone levels further, which will explain a corresponding decrease in breast density. Our research results will have significant implications for breast cancer risk reduction. Reducing breast density can be expected to reduce the volume of target tissue at risk for breast cancer development and will improve the sensitivity of mammography for screening. The study may lead to a novel, non-invasive and economical approach to breast cancer prevention.