HT, Mammographic Densites and Breast Cancer

项目C：HT，乳腺摄影密度和乳腺癌。有越来越多的流行病， 实验和临床证据表明，激素治疗与雌激素和孕激素（EPT）的绝经期 女性患乳腺癌的风险比单独使用雌激素治疗更高。妇女的结果 健康倡议的临床试验有力地证实了这一点。然而，一些临床上重要的问题仍然存在， 这是一个有待解决的问题，特别是确定哪些妇女在使用EPT时患乳腺癌的风险最高。 只有一小部分女性在开始EPT时会发生乳房X线密度变化。以来 乳腺摄影密度是一个重要的乳腺癌预测因子，重要的是要确定这是否是一个重要的因素。 女性的一个子集是那些谁将发展乳腺癌的结果，EPT，如果是这样，什么是 决定因素，包括遗传因素，乳房X线摄影密度变化。明显 候选基因是那些编码代谢、运输和反式激活中重要酶的基因 EPT的活动。我们以前发现，血清雌酮水平的变化预测乳房X线检查 随机分配至EPT组的女性的密度变化。我们也有一些初步证据表明， 与激素水平增加相关的因素可能预测谁会发展这种乳房X光检查。 密度增加。本拟议项目将在这些早期研究结果的基础上加以扩展。我们提出了一个基因 一项流行病学研究，利用正在进行的加州教师研究（CTS），一个队列， 教师和行政人员在加州，有相对统一的健康保险和高 乳房X光检查率。该项目的主要具体目标是确定是否选择 编码在EPT的代谢、转运或活性中重要的酶的基因的变体预测1） 绝经后开始EPT治疗的女性乳房X线摄影密度增加，2）乳腺 癌症风险。第二个目标是确定3）这些基因变异是否能预测乳腺癌 EPT使用者的风险和4）乳腺癌的风险与乳腺摄影密度增加有关 开始使用EPT后。目标1将在来自CTS的1000名EPT初学者的教师队列中进行评估， 而目标2 - 4将在一项来自CTS的巢式病例对照研究中解决， 癌症病例和900名对照。如果成功的话，这个提议可能会有很大的临床意义，因为它可以 帮助我们了解在乳腺癌易感性方面谁可以安全使用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.