Mammographic Breast Density and Ovarian Cancer

描述(申请人提供)：卵巢癌是美国女性第二常见的妇科癌症，但通常在晚期确诊，是2008年妇科癌症死亡的主要原因。在缺乏有效和广泛的卵巢癌筛查的情况下，确定卵巢癌的新危险因素，并通过另一种癌症筛查工具-乳房X光检查--进行评估，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做过一次乳房X光检查。除了检测乳腺癌，乳房X光检查还可以评估乳房X光检查的乳房密度。乳房X光检查的乳房密度是乳腺癌的最大风险因素之一--乳房密度较大的女性患乳腺癌的风险是乳房密度较小的女性的3-6倍。乳房X光摄影密度被认为是累积雌激素暴露的一个标志。然而，乳房密度尚未被评估为卵巢癌的风险因素，尽管它与乳腺癌有共同的荷尔蒙病因。7、8乳房X光检查乳房密度--如果与卵巢癌有关--将是临床上可行和有效的方法，以确定潜在的卵巢癌高危女性。该项目的具体目标是：1)评估1996-2008年期间参加乳腺癌监测联盟的40-79岁女性中乳房X光检查的乳房密度与卵巢癌发病风险之间的关系；2)确定乳房X光检查的乳房密度与卵巢癌风险之间的关系是否受到卵巢癌危险因素的影响，包括生育、激素治疗、口服避孕药的使用、乳腺癌或卵巢癌的家族史以及更年期状态。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的，BCSC是一个全国性的多地点美国妇女队列和社区实践中的乳房X光检查。到目前为止，BCSC已经积累了来自220多万名妇女的860多万张乳房X光照片，诊断出100多万例乳腺癌。我们预计在1996-2008年间确定3200多例卵巢癌病例，并进行平均8年的随访。根据BI-RADS(R)密度分级标准，放射科医生在乳房X光检查时评估乳房密度：1类，几乎全是脂肪；2类，散在纤维腺密度；3类，不均匀密度；4类，极高密度。我们将使用COX比例风险模型来估计与乳腺密度类别相关的卵巢癌的调整风险比。我们将评估卵巢癌危险因素的影响修正，并检验与似然比检验的交互作用。这项应用的新颖性在于，通过一种短、低影响和低成本的干预措施-乳房X光摄影筛查的乳房密度-潜在地提高了卵巢癌筛查的能力。乳房X光摄影有可能不仅有助于我们对乳腺癌的临床了解，而且还可能为卵巢癌提供信息。 公共卫生相关性：该项目的目的是确定在乳房X光检查中判断的乳房密度是增加还是降低乳腺癌监测联盟中女性患卵巢癌的风险。我们还将研究某些女性群体是否比其他女性更有可能患上卵巢癌。这是一项重要的研究，因为卵巢癌的新风险因素很少，而且我们可能会确定一个风险因素，该因素也可以通过乳房X光检查进行测量，这对许多美国女性来说将是重要的。

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.