Mammographic Density and Risk of Contralateral Breast Cancer

描述（由申请人提供）：乳腺摄影密度（MD）是第一原发性乳腺癌的一个公认的强风险因素。患有一侧乳腺浸润性癌的女性患对侧乳腺癌（CBC）的风险比一般人群患原发性乳腺癌的风险高2-5倍。我们和其他研究人员已经表明，女性在第一次接受的治疗可以改变她患CBC的风险。研究表明，MD在对一些激素和其他治疗的反应中改变，随着绝经期雌激素和孕激素治疗而增加，随着他莫昔芬（一种抗激素治疗以及化疗）而减少。这是合理的，MD，治疗前和治疗后，可能是有用的临床标志物的风险CBC的妇女与第一原发性乳腺癌。由于筛查和治疗的改善，乳腺癌幸存者的数量越来越多。然而，很少有已知的临床决定因素，随后CBC，限制妇女和卫生保健提供者在评估和管理这种风险。 正在进行的妇女环境、癌症和辐射流行病学（WECARE）II研究是一项以人群为基础的研究，目前正在招募和采访800例CBC病例和800例单侧乳腺癌（UBC）对照，沿着审查他们的乳腺癌诊断和治疗病历。我们现建议：检索首次乳腺癌诊断时或诊断前一年内拍摄的乳房X线照片和诊断后12-18个月拍摄的乳房X线照片;使用成熟的标准阈值法（Cumulus）和新型自动密度测量（Variation或“V”）定量评估MD。我们的主要目标是：1。估计在首次诊断时（在或直到一年前）左右对侧乳房的MD（%MD和绝对致密面积两者，使用积云阈值程序）与对侧乳房中CBC浸润性乳腺癌的后续诊断的风险之间的关系; 2.估计初始诊断后12-18个月（当初始化疗和放疗可能完成时）对侧乳腺的MD（%MD和致密区域，使用积云）与对侧乳腺中浸润性乳腺癌的后续诊断风险之间的关系;以及3.按治疗方式评估治疗前后（和/或开始激素治疗后）对侧乳房MD的变化。我们的第二个具体目标是：1。评估治疗前后对侧乳腺MD（%MD或致密面积）的变化是否与对侧乳腺浸润性乳腺癌的后续诊断风险相关; 2.使用V（一种自动化、经验证的乳腺密度测量）解决上述目标，并将结果与来自积云测量的结果进行比较。我们提出的这项新研究可能有助于识别CBC高风险的女性，它解决了一个未充分研究的问题，这个问题对许多在第一次原发性乳腺癌中幸存的女性具有高度的临床重要性。

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.