Mammographic Density & Prognosis among Breast Cancer Intrinsic Subtypes

描述（由申请人提供）：乳腺摄影密度是乳腺癌发生的最强风险因素之一。它被认为部分反映了乳腺上皮细胞和基质细胞的增殖状态，并已发现与某些内源性激素和生长因子的水平有关。它通过他莫昔芬治疗和促性腺激素释放激素激动剂降低，通过使用雌激素加孕酮增加。因此，乳腺摄影密度可能与乳腺癌的风险和进展有关。一些非常小的研究表明，乳腺摄影密度可以预测浸润性乳腺癌患者的复发。我们的主要目标是确定在Kaiser Permanente北方加州（KPNC）健康计划成员中，诊断浸润性乳腺癌时的乳腺摄影密度是否可预测参与两个大型且特征明确的基于人群的队列（LACE和Pathways）的患者随后发生乳腺癌事件的风险。由于患者的可用性（例如，年龄、体重指数、人种/种族）、临床（例如，疾病阶段、治疗）和行为因素（例如，体重减轻），以及用于将癌症分类为内源亚型的肿瘤标志物数据。在KPNC，成员几乎从计划中获得所有的医疗保健。此外，医疗记录的所有内容，包括乳房X线照片，都被无限期地存储，并可用于IRB批准的研究。具体目标是：1）检查乳腺摄影密度与乳腺癌内在亚型之间的关系; 2）检查乳腺摄影密度与复发风险和新原发病之间的关系; 3）检查乳腺摄影密度与预后之间的关系是否因内在亚型而异; 4）检查开始辅助他莫昔芬后密度的变化是否预测治疗益处。这将是迄今为止对浸润性乳腺癌患者的乳腺摄影密度和预后的最大规模研究。它也是第一个将乳腺摄影密度的联合收割机测量与使用50个基因测定的肿瘤分子分类相结合，使我们能够检查乳腺密度和预后的关联是否因内在亚型而异。

DESCRIPTION (provided by applicant): Mammographic density is one of the strongest risk factors for the development of breast cancer. It is thought in part to reflect the proliferative stte of epithelial and stromal cells in the breast and has been found to be associated with levels of some endogenous hormones and growth factors. It is reduced by tamoxifen therapy and by a gonadotropin-releasing hormone agonist and is increased with use of estrogen plus progesterone. Mammographic density, therefore, may be associated with both the risk and progression of breast cancer. A few, very small studies suggest mammographic density may predict recurrence among patients with invasive breast cancer. Our primary goal is to determine whether mammographic density at diagnosis of invasive breast cancer predicts risk of subsequent breast cancer events among patients participating in two large and well-characterized population-based cohorts (LACE and Pathways) within the Kaiser Permanente Northern California (KPNC) health plan membership. The combined LACE and Pathways cohorts are an ideal study population for this proposal because of the availability of patient (e.g, age, body mass index, race/ethnicity), clinical (e.g., disease stage, treatment) and behavioral factors (e.g., weight loss), as well as tumor marker data for classification of cancers into intrinic subtypes. At KPNC, members receive virtually all their health care from the plan. Further, all contents of the medical record, including mammograms, are stored indefinitely and are available for IRB- approved research. The specific aims are to: 1) Examine the association between mammographic density and breast cancer intrinsic subtypes; 2) Examine the association between mammographic density and risk of recurrence and new primary disease; 3) Examine whether the association between mammographic density and prognosis varies by intrinsic subtype; and 4) Examine if change in density after initiation of adjuvant tamoxifen predicts treatment benefit. This will be the largest study to date on mammographic density and prognosis in patients with invasive breast cancer. It also is the first to combine measures of mammographic density with molecular classification of tumors using a 50-gene assay, enabling us to examine whether associations of breast density and prognosis vary by intrinsic subtype.