Mammographic Breast Density and Ovarian Cancer

描述（由申请人提供）：卵巢癌是美国女性第二常见的妇科癌症，但通常在晚期诊断，是2008年妇科癌症死亡率的主要原因。在缺乏有效和广泛的卵巢癌筛查的情况下，通过另一种癌症筛查工具-乳房X线检查来确定卵巢癌的新风险因素可能对该领域具有相当大的价值。大多数美国成年女性报告至少有一次乳房X光检查。除了检测乳腺癌外，乳房X光检查还可以评估乳房X光检查的乳腺密度。乳房X光密度是乳腺癌最强的危险因素之一，与乳房密度较低的女性相比，乳房密度较高的女性患乳腺癌的风险增加3-6倍。乳腺密度被认为是累积雌激素暴露的标志。然而，乳腺密度尚未被评估为卵巢癌的风险因素，即使它与乳腺癌有共同的激素病因学。7，8乳房X线摄影乳腺密度-如果与卵巢癌相关-将是临床上可行的和有效的方法，以确定妇女潜在的卵巢癌高风险。该项目的具体目标是：1）估计1996-2008年期间参加乳腺癌监测联盟的40-79岁妇女中乳房X线摄影乳腺密度与卵巢癌发病风险之间的关联;和2）确定乳房X线摄影乳腺密度和卵巢癌发病风险之间的关联是否被卵巢癌风险因素改变，包括产次，激素治疗使用、口服避孕药使用、乳腺癌或卵巢癌家族史和绝经状态。我们建议在参加乳腺癌监测联盟（BCSC）的一组妇女中调查这些目标，BCSC是一个美国妇女和社区实践中乳房X线摄影的国家多站点队列。迄今为止，BCSC已从220多万名妇女那里积累了860多万张乳房X线照片，诊断出10多万例乳腺癌。我们预计在1996年至2008年期间将确定超过3,200例卵巢癌病例，平均随访8年。由放射科医生在乳房X线摄影时根据BI-RADS（R）密度量表评估乳腺密度：1类，几乎完全是脂肪; 2类，分散的纤维腺体密度; 3类，不均匀致密; 4类，极致密。我们将使用考克斯比例风险模型来估计与乳腺密度类别相关的卵巢癌的校正风险比。我们将评估卵巢癌危险因素对效应的影响，并使用似然比检验检验相互作用。该应用的新奇在于通过短时间、低影响、低成本的干预--乳腺X线摄影筛查的乳腺密度--来改善卵巢癌筛查的潜在能力。乳房X光检查不仅可以用于告知我们对乳腺癌的临床理解，而且还可以为卵巢癌提供信息。 公共卫生相关性：该项目的目的是确定乳腺X线摄影判断的乳腺密度是否增加或减少乳腺癌监测联盟中妇女患卵巢癌的风险。我们还将研究某些女性群体是否比其他女性更容易患卵巢癌。这是一项重要的研究，因为卵巢癌几乎没有新的风险因素，我们可能会发现一个风险因素，也可以在乳房X光检查中测量，这对许多美国女性来说很重要。

DESCRIPTION (provided by applicant): Ovarian cancer is the second most common gynecologic cancer in US women, but often diagnosed at a late stage, it is the leading cause of gynecologic cancer mortality in 2008. In the absence of effective and widespread ovarian cancer screening, identifying a new risk factor for ovarian cancer, which is assessed through another cancer screening tool---mammography-could be of considerable value to the field. The majority of US adult women report having at least one mammogram. In addition to detecting breast cancer, mammograms allow assessment of mammographic breast density. Mammographic breast density is one of the strongest risk factors for breast cancer-a 3-6-fold increased risk of breast cancer in women with denser breasts compared to women with less dense breasts. Mammographic breast density is believed to be a marker for cumulative estrogen exposure. However, breast density has not yet been evaluated as a risk factor for ovarian cancer, even though it has a shared hormonal etiology with breast cancer.7, 8 Mammographic breast density-if related to ovarian cancer-would be a clinically feasible and efficient way of identifying women potentially at high-risk for ovarian cancer. The specific aims of this project are: 1) to estimate the association between mammographic breast density and incident ovarian cancer risk among women aged 40-79 years who participated in the Breast Cancer Surveillance Consortium during 1996-2008; and 2) to determine if the association between mammographic breast density and incident ovarian cancer risk is modified by ovarian cancer risk factors, including parity, hormone therapy use, oral contraceptive use, family history of breast or ovarian cancer, and menopausal status. We propose to investigate these aims in a cohort of women participating in the Breast Cancer Surveillance Consortium (BCSC), a national multi-site cohort of US women and mammography in community practice. To date, the BCSC has accumulated more than 8.6 million mammograms from over 2.2 million women and diagnosed more than 100,000 breast cancers. We expect to ascertain over 3,200 cases of incident ovarian cancer during 1996-2008, and an average of 8 years of follow-up. Breast density was assessed by the radiologist at the time of mammography according to BI-RADS(R) density scale: Category 1, almost entirely fatty; Category 2, scattered fibroglandular densities; Category 3, heterogeneously dense; and Category 4, extremely dense. We will use Cox proportional hazards modeling to estimate adjusted hazard ratios of ovarian cancer associated with breast density category. We will evaluate effect modification by ovarian cancer risk factors, and test for interaction with likelihood ratio test. The novelty of this application lies in the potential ability to improve screening for ovarian cancer through a short, low-impact, and low-cost intervention-breast density from mammography screening. There is the potential that mammography could be used not only to inform our clinical understanding of breast cancer, but could also be informative for ovarian cancer. PUBLIC HEALTH RELEVANCE: The purpose of this project is to determine whether breast density judged at mammography increases or decreases the risk of ovarian cancer among women in the Breast Cancer Surveillance Consortium. We will also look at whether certain groups of women are more likely to get ovarian cancer than other women. This is important research because there are few new risk factors for ovarian cancer, and we might identify a risk factor that is also measured at mammography, which would be important to many US women.