HT, Mammographic Densites and Breast Cancer

项目C：乳腺癌、乳腺摄影密度和乳腺癌。有越来越多的流行病， 雌激素和孕激素(EPT)治疗更年期的实验和临床证据 与单独使用雌激素治疗相比，女性增加乳腺癌的风险更大。女子单打比赛的结果 健康倡议临床试验强烈证实了这一点。然而，一些临床上重要的问题仍然存在。 需要解决的问题，特别是确定哪些妇女如果使用EPT，患乳腺癌的风险最高。 只有一小部分女性在开始EPT时会出现乳房X光密度变化。自.以来 钼靶密度是一个重要的乳腺癌预测指标，重要的是要确定这一点 作为EPT的结果，一部分女性会患上乳腺癌，如果是这样， 乳房X光摄影密度变化的决定因素，包括遗传决定因素。显而易见 候选基因是那些编码在新陈代谢、运输和转录激活中重要的酶的基因。 EPT活性。我们之前已经发现，血清雌酮水平的变化可以预测乳房X光检查 随机接受EPT的妇女的密度变化。我们也有一些试点证据表明基因 与激素水平升高相关的因素可能会预测谁会患上这种乳房X光检查 密度增加。这个拟议的项目将在这些早期发现的基础上进行扩展。我们正在提议一种基因 利用正在进行的加州教师研究(CTS)的流行病学研究，一组 加州的教师和管理人员拥有相对统一的医疗保险和较高的 乳房X光检查筛查率。这个项目的主要具体目标是确定是否选择了 编码EPT新陈代谢、运输或活性的重要酶的基因变异预测1) 绝经后和乳房接受EPT治疗的女性乳房X光密度增加 癌症风险。第二个目标是确定这些基因变异是否能预测乳腺癌 EPT使用者的风险和4)与乳房X光摄影密度增加相关的乳腺癌风险 在开始使用EPT之后。目标1将在1000名EPT初学者的CTS教师队列中进行评估， 虽然目标2-4将在一项来自CTS的嵌套病例对照研究中解决，该研究涉及大约900个乳房 癌症病例和900名对照。如果成功，这项提议可能会产生巨大的临床影响。 帮助我们了解在乳腺癌易感性方面，谁可以安全地使用EPT。

PROJECT C: HT, Mammographic Densities and Breast Cancer. There is growing epidemiologic, experimental, and clinical evidence that hormone therapy with estrogen and progestin (EPT) for menopausal women increases the risk of breast cancer more than estrogen treatment alone. Results from the Women's Health Initiative clinical trial strongly confirmed this. However, a number of clinically important issues remain to be solved, in particular to determine which women are at highest risk of breast cancer if they use EPT. Only a subset of women develop mammographic density change when they start EPT. Since mammographic density is an important breast cancer predictor, it is important to determine whether this subset of women are the ones who will develop breast cancer as a result of EPT, and if so, what the determinants, including the genetic determinants, of the mammographic density changes are. Obvious candidate genes are those that encode enzymes important in metabolism, transport, and transactivation activity of EPT. We have previously found that changes in serum estrone levels predict mammographic density changes in women randomized to EPT. We also have some pilot evidence suggesting that genetic factors associated with increases in hormone levels may predict who will develop such mammographic density increase. This proposed project will expand on these early findings. We are proposing a genetic epidemiologic study that takes advantage of the ongoing California Teachers Study (CTS), a cohort of teachers and administrators in California that have relatively uniform health coverage and high mammographic screening rates. The primary specific aims of this project are to determine whether selected variants in genes encoding for enzymes important in metabolism, transport, or activity of EPT predict 1) mammographic density increases in women who commence EPT treatment after menopause and 2) breast cancer risk. The secondary aims are to determine 3) whether these genetic variants predict breast cancer risk in EPT users and 4) the risk of breast cancer associated with increased mammographic density following start of EPT use. Aim 1 will be assessed in a cohort of teachers from CTS of 1000 EPT starters, while aims 2-4 will be addressed in a nested case-control study from CTS with approximately 900 breast cancer cases and 900 controls. If successful, this proposal could have large clinical implications as it could help us to understand who can safely use EPT in terms of breast cancer susceptibility.