Depo-Provera and Breast Cancer: Epidemiology/Pathology

描述（由申请人提供）：注射避孕药长效醋酸甲羟孕酮（DMPA）（Depo-Provera）是全球女性常用的避孕药，其含有与美国绝经后女性联合雌激素和孕酮激素治疗（CHT）方案中最常用的相同的孕酮。最近几项研究的数据表明，CHT会增加女性患乳腺癌的风险，而CHT中的β-胡萝卜素成分可能对这种增加的风险特别重要。然而，关于DMPA与乳腺癌风险之间关系的数据有限。现有证据表明，目前使用DMPA与乳腺癌风险增加1.5至1.65倍有关。然而，DMPA使用与乳腺癌之间的关系还需要进一步的研究，因为这些研究有方法学上的局限性（样本量和/或研究设计问题），均未在美国进行，因此尚不清楚这些结果是否适用于美国女性（因为生育和避孕模式因国家而异），并且对DMPA促进乳腺癌的机制知之甚少。即使我们发现DMPA和乳腺癌风险之间没有关联，这项研究也是值得的，因为在这种情况下，使用DMPA的女性可以放心，使用与乳腺癌有关的同一种药物作为注射避孕药时，不会增加乳腺癌的风险。 在此，我们提出了一项病例对照研究，其中包括1,000名年龄在20-44岁之间被诊断患有乳腺癌的妇女和1,000名居住在西雅图普吉特海湾地区的基于人群的对照。具体的假设是：（1）DMPA的使用与绝经前妇女乳腺癌的风险增加20-44？DMPA使用的持续时间和/或近期使用是否影响这种关联的程度？(2)人口统计学、生殖学或人体测量学特征，如胎次和体重指数，会改变这种关联吗？DMPA和乳腺癌风险之间的关联是否因组织学类型或类固醇受体（包括ERq、ERft和PR）的表达而异？

DESCRIPTION (provided by applicant): The injectable contraceptive depot medroxy-progesterone acetate (DMPA) (Depo-Provera) is commonly used by women worldwide, and it contains the same progestin that is most commonly used in combined estrogen and progestin hormonal therapy (CHT) regimens taken by postmenopausal women in the United States. Data from several recent studies indicate that CHT increases a woman's risk of breast cancer, and that the progestin component of CHT may be particularly important with respect to this increased risk. There are limited data on the relationship between DMPA and breast cancer risk though. The available evidence suggests that current DMPA use is associated with a 1.5 to 1.65-fold increased risk of breast cancer. However, additional studies of the relationship between DMPA use and breast cancer are needed because these studies had methodologic limitations (sample size and/or study design issues), none were conducted in the U.S. and so it is unclear whether or not these results are generalizable to U.S. women (since reproductive and contraceptive patterns vary widely by country), and little is known about mechanisms through which DMPA promotes breast cancer. This study is worthwhile even if we find that there is no association between DMPA and breast cancer risk, since in this case women using DMPA will be reassured that using the same drug that has been implicated as a cause of breast cancer does not also increase their breast cancer risk when taken as an injectable contraceptive. Herein we propose a case-control study of 1,000 women aged 20-44 who have been diagnosed with breast cancer and 1,000 population-based controls who reside in the Seattle-Puget Sound area. The specific hypotheses to be tested are: (1) Is DMPA use associated with an increased risk of breast cancer in premenopausal women 20-44? Does the duration and/or recency of DMPA use influence the magnitude of this association?; (2) Do demographic, reproductive, or anthropometric characteristics, such as parity and body mass index, modify this association?; and (3) Does the association between DMPA and breast cancer risk vary by histologic type or by the expression of steroid receptors including ERq, ERft, and PR?