Mammographic Density and Soy Isoflavones

描述（由申请人提供）：食用高水平大豆的人群，如在许多亚洲国家，与食用典型西方饮食的人群相比，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，当绝经前妇女食用含有弱雌激素异黄酮的豆浆提供15%的能量时，她们的卵巢激素水平最低。未观察到不良反应。进一步的问题是异黄酮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（如乳腺密度）来做到这一点。乳房致密的女性患乳腺癌的风险高出4-6倍。此外，更大的乳腺密度使得通过乳房x光检查发现早期乳腺癌更加困难。为了验证食用大豆异黄酮降低乳腺密度的假设，我们提出了一项随机双盲研究，两组，每组100名绝经前妇女。研究人员将招募乳腺组织密度为50%的女性，随机分配服用大豆异黄酮药片（治疗组）或不含异黄酮的安慰剂药片（对照组）2年。每天的总异黄酮剂量为150毫克。妇女将在补充干预期之前和期间提供血液和尿液样本，用于卵巢激素和异黄酮的分析。在基线和干预期结束后，受试者将通过乳房x光摄影和磁共振成像检查乳房密度。干预的有效性将通过比较两组在2年干预期间致密乳腺组织的平均变化，并调整基线值和感兴趣的个体患者特征来确定。我们假设，绝经前妇女服用1至2年的大豆异黄酮补充剂会降低内源性雌激素的影响，并进一步降低黄体酮水平，这将解释乳腺密度相应降低的原因。我们的研究结果将对降低乳腺癌风险具有重要意义。降低乳腺密度有望减少有乳腺癌发展风险的靶组织的体积，并将提高乳房x光检查的灵敏度。这项研究可能会带来一种新的、非侵入性的、经济的乳腺癌预防方法。

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.