Mammographic Breast Density and Ovarian Cancer

描述（由申请人提供）：卵巢癌是美国女性第二大常见妇科癌症，但通常在晚期才被诊断出来，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光检查——确定卵巢癌的新危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密度。乳房x光检查的乳房密度是乳腺癌的最大危险因素之一——乳房密度高的女性患乳腺癌的风险是乳房密度低的女性的3-6倍。乳房x线摄影乳房密度被认为是雌激素累积暴露的标志。然而，乳腺密度尚未被评估为卵巢癌的危险因素，尽管它与乳腺癌有共同的激素病因。7,8乳房x线摄影的乳腺密度——如果与卵巢癌有关的话——将是一种临床可行且有效的方法来识别潜在的卵巢癌高危女性。该项目的具体目的是：1)估计1996-2008年期间参加乳腺癌监测联盟的40-79岁妇女的乳房x光检查乳房密度与卵巢癌发病风险之间的关系；2)确定乳腺密度与卵巢癌发生风险之间的关系是否受到卵巢癌危险因素的影响，包括胎次、激素治疗使用、口服避孕药使用、乳腺癌或卵巢癌家族史以及绝经状态。我们建议在参加乳腺癌监测联盟（BCSC）的女性队列中调查这些目标，BCSC是美国妇女和社区实践中的乳房x光检查的国家多站点队列。迄今为止，BCSC已从220多万名妇女中收集了860多万张乳房x光片，并诊断出10万多例乳腺癌。我们期望在1996-2008年期间确定超过3200例卵巢癌病例，平均随访8年。乳房密度由乳房x光检查时的放射科医生根据BI-RADS(R)密度量表评估：1类，几乎完全是脂肪；第2类，散在纤维腺密度；第3类，非均匀致密；第4类，密度极高。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校正风险比。我们将评价卵巢癌危险因素对效果的影响，并用似然比检验检验其相互作用。该应用的新颖之处在于，通过短时间、低影响、低成本的干预——乳房x线摄影筛查，提高卵巢癌筛查的潜在能力。乳房x光检查不仅可以帮助我们了解乳腺癌的临床情况，还可以为卵巢癌提供信息。

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.