Mammographic Density and Risk of Contralateral Breast Cancer

描述（由申请人提供）：乳房x线摄影密度（MD）是一种公认的原发性乳腺癌的强烈危险因素。患侵袭性乳腺癌的女性患对侧乳腺癌（CBC）的风险是患原发性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，女性第一次接受的治疗可以改变她患CBC的风险。研究表明，MD会因一些激素和其他治疗而改变，绝经期雌激素和黄体酮治疗会增加MD，而他莫昔芬（一种抗激素治疗和化疗）会减少MD。治疗前后的MD可能是诊断原发性乳腺癌患者罹患CBC风险的有用临床标志物。由于筛查和治疗的改进，乳腺癌幸存者的人数不断增加。然而，很少有已知的临床决定因素随后的CBC，限制了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研究是一项基于人群的研究，目前正在招募和访问800例CBC病例和800例单侧乳腺癌（UBC）对照，同时审查其乳腺癌诊断和治疗医疗记录。我们现在建议：检索第一次乳腺癌诊断时或诊断前一年内以及诊断后12-18个月的乳房x光照片；数字化胶片乳房x线照片；并使用完善的标准阈值方法（Cumulus）和一种新的自动密度测量方法（Variation或“V”）对MD进行定量评估。我们的主要具体目标是：1。评估首次诊断前后（1年前或1年前）对侧乳腺的MD （MD %和绝对密度面积，使用Cumulus阈值程序）与随后对侧乳腺CBC浸润性乳腺癌诊断风险之间的关系；2. 评估初始诊断后12-18个月（当初始化疗和放疗可能完成时）对侧乳腺的MD （MD %和密集区，使用Cumulus）与随后对侧乳腺浸润性乳腺癌诊断的风险之间的关系；和3。通过治疗方式评估治疗前后（和/或激素治疗开始后）对侧乳腺MD的变化。我们的次要具体目标是：1。评估治疗前后对侧乳腺MD （%MD或致密区）的变化是否与随后对侧乳腺浸润性乳腺癌诊断的风险相关；2.为了解决上述目的，使用V，一个自动化的，有效的，乳房密度测量和比较结果与那些从积云测量得出的。我们提出的这项新研究可能有助于识别CBC高风险女性，它解决了一个未被充分研究的问题，这对许多首次原发性乳腺癌存活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.