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

伴或不伴 DCIS 的浸润性乳腺癌：种族、危险因素和结果

基本信息

批准号：
8512328
负责人：
Christine B. Ambrosone
金额：
$ 8.5万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8512328
关键词：
Affect African African American Aggressive course American Area Biological Breast Breast Cancer Risk Factor Case-Control Studies Characteristics Chemoprevention Clinical Cox Proportional Hazards Models Data Data Set Databases Decision Making Development Diagnosis Disease Disease Outcome Epidemiologist Estrogen receptor negative Estrogen receptor positive Etiology European Evaluation Event FLT1 gene Fibroblast Growth Factor 2 Freezing Genes Genetic Goals Health Histology Hormonal Immunohistochemistry In Situ Indolent Insulin-Like Growth Factor I Interdisciplinary Study Interferons Interleukin-6 Knowledge Lesion Literature MMP11 gene Malignant - descriptor Malignant Neoplasms Mammary Neoplasms Mammography Measures Noninfiltrating Intraductal Carcinoma Operative Surgical Procedures Outcome PTGS2 gene Pathway interactions Patients Phenotype Population Study Positive Lymph Node Prevention Process Prognostic Factor Proteins Race Recurrence Research Risk Factors Role Roswell Park Cancer Institute Sampling Socioeconomic Status Subgroup Suggestion TNF gene Therapeutic Time Tissue Inhibitor of Metalloproteinase-3 Tissue Sample Treatment outcome Tumor Tissue Visit Woman carcinogenesis clinically significant cohort design disease characteristic experience follow-up infiltrating duct carcinoma interdisciplinary approach malignant breast neoplasm molecular phenotype mortality novel outcome forecast prognostic programs protein expression public health relevance reproductive research study screening tumor

项目摘要

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.

描述（由适用提供）：几乎没有进行研究以确定纯粹的浸润性导管癌（IDC）是否没有伴随的导管癌（DCIS）是否与病因学，预后，微环境中的DCIS与DCIS的混合IDC有所不同，尽管在文献方面有一些建议，即纯粹有可能出现一些建议。这项拟议的研究的目的是对这种现象进行彻底检查。我们将使用病例对照研究（n = 3715）的数据来检查纯IDC与混合IDC与DCI的混合IDC与DCI的危险因素，旨在检查非裔美国和欧美妇女中早期/侵略性乳腺癌的预测因子。我们将首先确定纯IDC在AA中是否比EA女性更常见，并表征两种表型相关的肿瘤特征。考虑到与社会经济状况和筛查有关的因素，将检查危险因素，尤其是生殖因素和马匹因素。然后，在1995年至2005年在罗斯威尔公园癌症研究所接受治疗的1588名妇女中，并随后进行了治疗结果，我们将研究肿瘤与疾病特征与纯粹的IDC之间的关联，以及与DCIS混合IDC。 COX比例危害建模将用于确定这两个群体中女性的疾病和治疗结果，并考虑接受其他疾病特征和治疗。我们假设拥有纯粹IDC的女性比与DCIS混合IDC的女性更有可能具有侵略性的肿瘤特征，并且具有更多的回报和更短的生存时间。最后，在使用库存的冷冻组织样品的探索性分析中，我们将从15名具有纯IDC女性和15名具有DCIS混合IDC的女性的肿瘤中进行显微解剖的基质组织，并使用实时定量PCR来检查IL-6，TNF--？ TIMP-3在每组中以其在肿瘤发育中的作用而闻名。这项由流行病学家和乳房生物学家领导的拟议的多学科研究将是第一个通过祖先研究分布f纯IDC和与DCI混合的分布的人，并检查每个途径的风险因素，这是一个以前出乎意料的领域。在大型数据集中，我们将评估这些临床亚组的预后意义，并在探索性试点分析中，我们将研究基质微环境中特定途径在IDC中有助于有和无合一致性DCI的IDC病理生物学差异的机制。