Mammographic Density and Risk of Contralateral Breast Cancer

描述(申请人提供)：乳房X光摄影密度(MD)是一个公认的和强烈的风险因素，首次原发性乳腺癌。患有一侧乳腺浸润性癌的女性患对侧乳腺癌(CBC)的风险是第一次原发乳腺癌的一般人群风险的2-5倍。我们和其他研究人员已经证明，女性在第一次初选中接受的治疗可以改变她患CBC的风险。研究表明，一些激素和其他治疗会改变MD，更年期雌激素和黄体酮治疗会增加MD，他莫昔芬(一种抗激素治疗和化疗)会减少MD。无论是治疗前还是治疗后，MD都可能是首次发生乳腺癌的女性CBC风险的有用临床标记物。由于筛查和治疗的改进，乳腺癌幸存者的数量不断增加。然而，几乎没有已知的后续CBC的临床决定因素，限制了妇女和卫生保健提供者在评估和管理这一风险方面的作用。正在进行的妇女环境、癌症和辐射流行病学(WeCare)II研究是一项基于人群的研究，涉及800名CBC病例和800名单侧乳腺癌(UBC)对照患者，目前正在招募和采访他们，并审查他们的乳腺癌诊断和治疗医疗记录。我们现在建议：检索在第一次乳腺癌诊断时或在诊断前一年内拍摄的乳房X光照片，以及诊断后12-18个月拍摄的乳房X光照片；数字化胶片乳房X光照片；并使用公认的标准阈值方法(Cumulus)和一种新的自动密度测量方法(Variable或“V”)对MD进行定量评估。我们的主要目标是：1.估计对侧乳房在首次诊断时(早于或最早一年)的MD(%MD和绝对密度区)与随后诊断CBC浸润性乳腺癌的风险之间的关系；2.估计初诊后12-18个月(最初的化疗和放疗可能完成时)对侧乳腺MD(%MD和致密区)与随后诊断为浸润性乳腺癌的风险之间的关系；3.通过治疗方法评估治疗前后(和/或激素治疗开始后)对侧乳房MD的变化。我们的次要目标是：1.评估对侧乳房治疗前后MD(%MD或致密区)的变化是否与随后诊断为对侧乳腺浸润性乳腺癌的风险有关；2.使用自动、有效的乳房密度测量V来解决上述目标，并将结果与从积云测量得出的结果进行比较。我们提出的这项新研究可能有助于确定CBC的高危女性，它解决了一个对许多在第一次原发乳腺癌中幸存下来的女性具有高度临床重要性的未被研究的问题。 公共卫生相关性：患有第一次原发浸润性乳腺癌的妇女在对侧乳房(CBC)发生第二次原发乳腺癌的风险很高。乳房X线摄影密度(MD)是一种公认的、具有很强可变性的初发乳腺癌危险因素。本研究旨在确定MD是否可以作为CBC风险的标志物，从而为影响临床治疗和改善预后提供新的机会。我们提出了一项新的研究，对许多在第一次原发乳腺癌中幸存下来的女性具有很高的临床重要性。

DESCRIPTION (provided by applicant): Mammographic density (MD) is a well-established and strong risk factor for first primary breast cancer. Women with invasive cancer in one breast are at 2-5 times higher risk of developing a contralateral breast cancer (CBC) compared to the general population risk of a first primary breast cancer. We and other researchers have shown that the treatment a woman receives for her first primary can alter her risk of developing CBC. Studies show MD is altered in response to some hormonal and other treatments, increasing with menopausal estrogen and progesterone therapy, and decreasing with tamoxifen, an anti-hormonal treatment as well as chemotherapy. It is plausible that MD, both before and after treatment, may be useful clinical markers of risk of CBC in women with a first primary breast cancer. As a result of improved screening and treatment, there are increasing numbers of survivors of breast cancer. However, there are few known clinical determinants of subsequent CBC, limiting women and health care providers in the assessment and management of this risk. The ongoing Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) II Study is a population-based study of 800 CBC cases and 800 unilateral breast cancer (UBC) controls currently being recruited and interviewed, along with having their breast cancer diagnosis and treatment medical records reviewed. We now propose to: retrieve mammograms taken at, or within a year prior to, the first breast cancer diagnosis and those at 12-18 months following diagnosis; digitize film mammograms; and quantitatively assess MD using both the well-established standard thresholding method (Cumulus) and a novel automated density measure (Variation or "V"). Our Primary Specific Aims are: 1. To estimate the relationship between MD (both %MD and absolute dense area, using the Cumulus thresholding program) of the contralateral breast around the time of the first diagnosis (at or up to one year prior) and the rik of a subsequent diagnosis of CBC invasive breast cancer in the contralateral breast; 2. To estimate the relationship between MD (both %MD and dense area, using Cumulus) of the contralateral breast at 12-18 months following initial diagnosis (when initial chemotherapy and radiation treatments are likely completed) and the risk of a subsequent diagnosis of invasive breast cancer in the contralateral breast; and 3. To assess changes in MD of the contralateral breast before and after treatment (and/or after initiation of hormonal treatment) by treatment modality. Our Secondary Specific Aims are: 1. To estimate whether change in MD (%MD or dense area) of the contralateral breast before and after treatment is associated with risk of a subsequent diagnosis of invasive breast cancer in the contralateral breast; 2.To address the above Aims using V, an automated, validated, breast density measurement and compare results with those derived from the Cumulus measure. The novel study we propose could be useful for identifying women at high risk of CBC and it addresses an understudied issue that is of high clinical importance to the many women who survive their first primary breast cancer. PUBLIC HEALTH RELEVANCE: Women with a first primary invasive breast cancer are at high risk of developing a second primary breast cancer in the contralateral breast (CBC). Mammographic density (MD) is a well-established and strong modifiable risk factor for first primary breast cancer. This study aims to determine whether MD can be used as a marker of risk of CBC, thus providing new opportunities to influence clinical management and improve outcomes. We propose a novel study that is of high clinical importance to the many women who survive their first primary breast cancer.