Sex Steroids & Mammographic Density in the Postmenopause

说明(申请人提供)：较高的乳房X光照相密度是乳癌的独立风险因素，与乳房X光照相密度相关的风险程度高于几乎所有其他已知的乳癌风险因素。这项申请建议继续开展“绝经后性激素和乳房摄影密度”的工作，研究内源性和外源性类固醇对乳房X光摄影百分比密度的影响。这项研究是绝经后雌激素/孕激素干预(PEPI)试验的结果，该试验随机将绝经后妇女分为安慰剂、单纯雌激素或三种雌激素/孕激素联合治疗之一。到目前为止，“性激素和乳房摄影密度研究”的主要发现是：1)外源性雌激素治疗不影响平均乳房摄影密度，但在被分配到雌激素/孕激素治疗的3组中，乳房摄影密度显著增加；2)在三个雌激素/孕激素组中，治疗后血清雌酮水平的增加程度预示着乳房摄影密度的增加；以及3)内源性(治疗前)血清雌酮、雌二醇、孕酮和性激素结合球蛋白水平与乳房摄影密度呈正相关。基于这些发现，我们建议在这项研究中继续工作，以进一步了解乳房摄影密度的变化，特别是：1)哪些其他因素与基线(治疗前)乳房摄影密度有关？2)哪些其他因素可以预测治疗期间乳房X光检查密度的增加？我们假设激素(除已研究的激素外)、性激素生物合成/代谢途径中的遗传多态以及性激素受体中的基因多态将与激素治疗的基线乳腺摄影密度和/或乳腺摄影密度反应有关。拟议的续展项目将持续4年，将在加州大学洛杉矶分校和南加州大学进行。使用储存的样本，我们将测量基线和12个月的催乳素和孕激素水平。我们还将从存储的样本中提取DNA，以评估选定的遗传多态。在我们之前的工作中，已经测量了乳房X光密度结果数据和所有相关的协变量。我们将量化该项目中测量的荷尔蒙和遗传暴露与乳房X光摄影密度(基线以及基线和12个月之间的密度变化)之间的关系。

DESCRIPTION (provided by applicant): Higher mammographic density is an independent risk factor for breast cancer and the magnitude of risk associated with mammographic density is greater than that associated with almost all other known risk factors for breast cancer. This application proposes to continue work in "Sex Steroids and Mammographic Density in the Postmenopause", a study of the effects of endogenous and exogenous sex steroids on mammographic percent-density. This study is an outgrowth of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, which randomly assigned postmenopausal women to placebo, estrogen-only, or one of three combination estrogen/progestin treatments. To date, the principal findings of the "Sex Steroids and Mammographic Density Study" are: 1) Exogenous estrogen-only treatment did not affect mean mammographic density but significant increases in mammographic density did occur in 3 groups assigned to estrogen/progestin treatments; 2) In the three estrogen/progestin groups, but not in the estrogen-only group, the degree of increase in serum estrone level on-treatment predicted the amount of increase in mammographic density; and 3) Endogenous (pre-treatment) serum levels of estrone, estradiol, progesterone, and sex hormone binding globulin were positively associated with baseline mammographic density. Based on these findings, we propose to continue work in this study to gain a further understanding of variation in mammographic density, specifically: 1) What other factors are associated with baseline (pre-treatment) mammographic density? and 2) What additional factors predict increases in mammographic density during treatment? We hypothesize that hormones (in addition to those already studied), genetic polymorphisms in sex steroid biosynthetic/metabolic pathways, and genetic polymorphisms in sex steroid receptors will be related to baseline mammographic density and/or mammographic density response to treatment with hormone therapy. The proposed continuation project will last 4 years and will take place at UCLA and USC. Using stored samples, we will measure baseline and 12-month levels of prolactin and progestins. We will also extract DNA from stored samples to assess selected genetic polymorphisms. The mammographic density outcome data and all relevant covariates have already been measured during our prior work. We will quantify the relations between the hormone and genetic exposures measured in this project and mammographic density (at baseline as well as change in density between baseline and 12 months).