Molecular Profiles and Lifestyle Factors in Breast Cancer Prognosis

描述（由申请人提供）：近年来，新技术使我们能够更好地表征乳腺癌的异质性，并根据其分子特征识别许多生物学亚型。因此，肿瘤的分子分类越来越多地用于指导治疗选择和新治疗开发，评估预后和病因学研究。一种分子分类，即“内在亚型”，其基于乳腺癌的起源细胞类型（管腔A/B或基底）或肿瘤是否为HER 2阳性来区分乳腺癌，已用于鉴定生物学和临床上不同的乳腺癌亚型。本提案的主要目的是在北方加州Kaiser Permanente（KPNC）医疗护理项目内进行的两项正在进行的乳腺癌幸存者（N=4177）队列研究中，检查内在亚型的影响及其与乳腺癌风险因素和短期和长期预后的关系。第一项研究，癌症后生活流行病学（LACE）队列，一个基于人群的队列，包括2，288名诊断为I期>1 cm，II期或IIIa期乳腺癌的女性，于2000- 2002年建立，以检查行为因素和乳腺癌预后。这些数据将与来自Pathways队列的1890例类似阶段的额外病例相结合，Pathways队列是一项于2006年1月开始的短期乳腺癌幸存者研究。考虑到迄今为止在能量相关因素和预后之间的发现中观察到的不一致性以及效果可能因肿瘤特征如激素受体状态而异的建议，这项建议的第二个目标是检查与能量平衡有关的特定行为是否可能与一般乳腺癌患者或主要是具有某些内在亚型的女性的预后有关。能量相关因素对短期预后的影响，该建议的另一个次要目标是继续随访LACE队列中的女性，直至诊断后15年，并检查能量相关生活方式因素与长期预后的关系。在诊断后的多个时间点收集关于体重、体重变化、体力活动和饮食的数据。每年通过自我报告并通过医疗记录和死亡证明核实，对妇女的复发和死亡情况进行跟踪。在拟议的新资助期间，将检索存档的肿瘤块，并使用免疫组织化学测定（IHC）将乳腺癌分类为内在亚型。这项研究将通过检查两个现有癌症幸存者队列中提出的问题来节省大量成本，这些癌症幸存者已经获得了诊断后的行为数据，并通过检索一个队列中的肿瘤标本来节省大量成本，其中接近90%的女性属于KPNC，HMO，肿瘤标本很容易获得。我们的提案解决了一系列问题，这些问题是癌症生存研究中新兴的优先领域，将对临床和公共卫生产生影响。

DESCRIPTION (provided by applicant): In recent years, new technologies have allowed us to better characterize the heterogeneity of breast cancer and to identify a number of biological subtypes based on their molecular profiles. Consequently, molecular classification of tumors is increasingly being used to guide treatment selection and new treatment development, in evaluating prognosis, and in studies of etiology. One molecular classification, the "intrinsic subtype", which distinguishes among breast cancers based on either their cell type of origin (luminal A/B or basal) or whether the tumor is HER2-positive, has been used to identify biologically and clinically distinct subtypes of breast cancer. The primary goal of this proposal is to examine the effects of intrinsic subtypes and their relationship to breast cancer risk factors and short and long-term prognosis in two ongoing cohort studies of breast cancer survivors (N=4177) being conducted within the Kaiser Permanente of Northern California (KPNC) Medical Care program. The first study, the Life After Cancer Epidemiology (LACE) cohort, a population-based cohort of 2,288 women diagnosed with Stage I>1 cm, II, or IIIa breast cancer, was established in 2000- 2002 to examine behavioral factors and breast cancer prognosis. These data will be combined with 1890 additional cases of similar stage from the Pathways cohort, a study of short term breast cancer survivors which began in January 2006. Given the inconsistency observed to date in findings between energy related factors and prognosis and the suggestion that effects may vary by tumor characteristics such as hormone receptor status, a secondary goal of this proposal is to examine whether specific behaviors related to energy balance may be related to prognosis among breast cancer patients in general or primarily among women with certain intrinsic subtypes Since most studies have only reported on effects of energy related factors on short term prognosis, another secondary goal of this proposal is to continue to follow women in the LACE cohort up until 15 year post-diagnosis and to examine the relationship of energy related lifestyle factors with long-term prognosis. Data on weight, weight change, physical activity and diet were collected at multiple time points post diagnosis. Women are followed annually for recurrence and death by self report and verified by medical record and death certificates. During the proposed new funding period, archived tumor blocks will be retrieved and, using immunohistochemical assays (IHC), breast cancers will be classified into intrinsic subtypes. This study will achieve tremendous cost savings by examining the proposed questions within two existing cohort of cancer survivors for whom post diagnosis data on behavior are already available and by retrieving tumor specimens within a cohort where close to 90% the women belong to the KPNC, an HMO, where tumor specimens are readily accessible. Our proposal addresses a range of issues that are emerging priority areas in cancer survivorship research which will have both clinical and public health impact.