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

描述（由申请人提供）：尽管文献中有一些建议认为单纯浸润性导管癌（IDC）可能具有更具侵袭性的病程，但很少有研究确定不伴导管原位癌（DCIS）的单纯浸润性导管癌（IDC）与伴DCIS的混合型IDC在病因、预后或微环境方面是否不同。这项研究的目的是对这一现象进行彻底的研究。我们将使用来自病例对照研究（n= 3715）的数据来检查纯IDC与混合IDC与DCIS的风险因素，该研究旨在检查非洲裔美国人和欧洲裔美国人女性中早期/侵袭性乳腺癌的预测因子。我们将首先确定单纯IDC在AA中是否比EA女性更常见，并描述两种表型的相关肿瘤特征。将检查风险因素，特别是生殖和激素因素，并考虑与社会经济地位和筛查相关的因素。然后，在1995年至2005年在Roswell Park癌症研究所接受治疗的1588名妇女的第二个队列中，我们将研究肿瘤和疾病特征与单纯IDC以及混合IDC与DCIS之间的关系。将使用考克斯比例风险模型来确定这两组女性的疾病和治疗结局，并考虑其他疾病特征和接受的治疗。我们假设，与单纯IDC的女性将更有可能有侵略性的肿瘤特征，并有更多的复发和较短的生存时间比混合IDC与DCIS的女性。最后，在使用冷冻组织样本库进行的探索性分析中，我们将显微解剖15名单纯IDC患者和15名IDC与DCIS混合患者的肿瘤间质组织，并使用实时定量PCR检测IL-6、TNF-α、IFN-β、考克斯-2、IGF-1、bFGF、TGF β-1、fmsFLT 1、MMP 11和TIMP-3，已知它们在肿瘤发展中的作用。这项由流行病学家和乳腺生物学家领导的多学科研究将首次调查纯IDC和混合IDC与DCIS的分布，并检查每种途径的风险因素，这是一个以前未探索的领域。在一个大的数据集中，我们将评估这些临床亚组的预后意义，并在探索性初步分析中，我们将研究基质微环境中的特定途径对伴或不伴DCIS的IDC的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.