Invasive breast cancer with and without DCIS: Race, risk factors and outcomes

描述(申请人提供)：尽管文献中有一些建议，单纯性浸润性导管癌(IDC)的病程可能更具侵袭性，但很少有研究确定单纯浸润性导管癌(IDC)是否与混合性IDC合并DCIS在病因、预后或微环境方面不同。这项拟议的研究的目的是对这一现象进行彻底的检查。我们将使用一项病例对照研究(n=3715)的数据来检验单纯IDC和混合IDC与DCIS的风险因素，该研究旨在检查非裔美国人和欧洲裔美国女性早期/侵袭性乳腺癌的预测因素。我们将首先确定单纯IDC在再障患者中是否比EA女性更常见，并确定这两种表型的相关肿瘤特征。将审查风险因素，特别是生殖和激素因素，同时考虑与社会经济地位和筛查有关的因素。然后，在1995年至2005年在罗斯威尔公园癌症研究所接受治疗并对治疗结果进行随访的1588名女性的第二个队列中，我们将检查肿瘤和疾病特征与单纯IDC以及混合IDC和DCIS之间的关系。考克斯比例风险模型将被用来确定这两组妇女的疾病和治疗结果，同时考虑其他疾病特征和接受的治疗。我们假设，与混合IDC和DCIS的女性相比，单纯IDC的女性更有可能具有侵袭性的肿瘤特征，复发率更高，生存时间更短。最后，在一项使用银行冷冻组织样本的探索性分析中，我们将显微解剖15名单纯IDC患者和15名混合性IDC合并DCIS患者的肿瘤间质组织，并使用实时定量聚合酶链式反应检测IL-6、TNF-β、干扰素-β、环氧合酶-2、IGF-1、碱性成纤维细胞生长因子、转化生长因子-1、fmsFLT1、MMP11和TIMP-3在每组患者中的表达水平。这项拟议的多学科研究由流行病学家和乳腺生物学家领导，将首次调查纯IDC和混合IDC与DCIS的祖先分布，并检查每条途径的危险因素，这是一个以前未被探索的领域。在一个大型数据集中，我们将评估这些临床亚组的预后意义，并在探索性先导分析中，我们将检查间质微环境中的特定通路对合并和不合并DCIS的IDC病理生物学差异的作用机制。

DESCRIPTION (provided by applicant): There has been little research conducted to determine if pure invasive ductal carcinoma (IDC) with no concomitant ductal carcinoma in situ (DCIS) differs from mixed IDC with DCIS in etiology, prognosis, or microenvironment, although there are some suggestions in the literature that pure IDC is likely to have a more aggressive course. The goal of this proposed research is to conduct a thorough examination of this phenomenon. We will examine risk factors for pure IDC vs mixed IDC with DCIS using data from a case- control study (n= 3715) designed to examine predictors of early/aggressive breast cancer in African-American and European-American women. We will first determine if pure IDC is more common in AA than in EA women, and characterize associated tumor characteristics for both phenotypes. Risk factors, particularly reproductive and hormonal factors, will be examined, with consideration of factors related to socioeconomic status and screening. Then, in a second cohort of 1588 women treated at Roswell Park Cancer Institute from 1995 to 2005 and followed up for treatment outcomes, we will examine associations between tumor and disease characteristics and pure IDC as well as mixed IDC with DCIS. Cox proportional hazard modeling will be used to determine disease and treatment outcomes among women in both of these groups, with consideration of other disease characteristics and treatments received. We hypothesize that women with pure IDC will be more likely to have aggressive tumor characteristics, and have more recurrences and shorter survival times than women with mixed IDC with DCIS. Finally, in an exploratory analysis using banked frozen tissue samples, we will microdissect stromal tissue from tumors from 15 women with pure IDC and 15 women with mixed IDC with DCIS and use real-time quantitative PCR to examine levels of expression of IL-6, TNF-¿, IFN-?, Cox-2, IGF-1, bFGF, TGF¿-1, fmsFLT1, MMP11 and TIMP-3, known for their role in tumor development, within each group. This proposed multidisciplinary research study, led by an epidemiologist and a breast biologist, will be the first to investigate the distribution f pure IDC and mixed IDC with DCIS by ancestry and to examine risk factors for each pathway, a previously unexplored area. In a large data set, we will evaluate the prognostic significance of these clinical subgroups, and in an exploratory pilot analysis, we will examine mechanisms by which specific pathways in the stromal microenvironment contribute to the pathobiological differences in IDC with and without concomitant DCIS.