Mammographic Density & Prognosis among Breast Cancer Intrinsic Subtypes

描述(申请人提供)：乳房X光摄影密度是乳腺癌发展的最大风险因素之一。它被认为在一定程度上反映了乳腺上皮细胞和间质细胞的增殖状态，并被发现与某些内源性激素和生长因子的水平有关。他莫昔芬治疗和一种促性腺激素释放激素激动剂可以降低它，而使用雌激素和黄体酮会增加它。因此，乳房X线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X光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浸润性乳腺癌诊断时的乳房X光摄影密度是否可以预测参与北加州凯撒永久医疗计划成员中两个大规模且具有良好特征的人群队列(LACE和Path)的患者随后发生乳腺癌事件的风险。基于患者(例如年龄、体重指数、种族/民族)、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在亚型的肿瘤标记物数据，LACES和Path联合队列是这项建议的理想研究人群。在KPNC，成员几乎所有的医疗保健都来自该计划。此外，医疗记录的所有内容，包括乳房X光照片，都被无限期存储，并可供IRB批准的研究使用。其具体目的是：1)检查乳房X光检查密度与乳腺癌固有亚型之间的联系；2)检查乳房X光检查密度与复发和新的原发疾病风险之间的联系；3)检查乳房X光检查密度和预后之间的联系是否因固有亚型而异；以及4)检查开始使用他莫昔芬后密度的变化是否可以预测治疗益处。这将是迄今为止关于浸润性乳腺癌患者钼靶密度和预后的最大规模的研究。它也是第一个使用50基因分析将乳房X光摄影密度测量与肿瘤分子分类相结合的方法，使我们能够检查乳房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.