Biomarkers of Tumor Initiation in Breast Cancer

乳腺癌肿瘤起始的生物标志物

基本信息

批准号：
8773669
负责人：
Deirdre Hill
金额：
$ 7.55万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8773669
关键词：
Address Adverse effects Antibodies Area Benign Biological Biological Factors Biological Markers Biopsy Breast Breast Cancer Prevention Breast Carcinogenesis Cell Cycle Clinical Trials Cytoskeleton Data Data Analyses Detection Development ERBB2 gene Elements Environment Epidemiologic Studies Epithelial Estrogen Receptors Event Extracellular Matrix Degradation Face Future Goals Grant Growth High Risk Woman Immunohistochemistry Inflammation Intervention Knowledge Lead Malignant - descriptor Malignant Neoplasms Mammary Gland Parenchyma Medical Surveillance Mesenchymal Methods Modeling Molecular Nested Case-Control Study New Mexico Pathologic Pathologist Pathway interactions Pilot Projects Population Population Heterogeneity Premalignant Prevention Prevention Research Process Proteins Protocols documentation Publications Publishing Raloxifene Risk Risk Assessment Risk Estimate Shapes Site Source Staining method Stains Systems Analysis Tamoxifen Tissue Microarray Tissues Validation Woman anticancer research cancer initiation cancer prevention cancer risk cancer stem cell carcinogenesis clinical risk cohort high risk hormone therapy improved information gathering lifestyle intervention malignant breast neoplasm molecular marker novel population based protein expression public health relevance sound statistics therapy development tool tumor tumor growth tumor initiation tumor microenvironment tumor registry tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): While a substantial proportion of women in the U.S. are considered at 'high risk' for breast cancer during their lifetime (Graubard 2010), most will never develop breast cancer. Women considered at high risk face mostly difficult choices to keep cancer at bay. Some are eligible for endocrine therapies such as Tamoxifen or Raloxifene, which have been associated with serious side effects in some users. Prevention options for high risk women are limited in part because our understanding of biological factors that cause breast cancer is fairly elementary. In addition, our current risk models only imprecisely estimate risk of subsequent cancer, and because effective and acceptable prevention options are scarce, most women at higher risk are not identified as such, or offered risk reducing therapies. Thus, there is a critical need to identify biomarkers in breast tissue that are related to subsequent risk, which may facilitate improved identification of women at high risk, and prompt development of therapies that are specific to their breast tissue changes. We propose to evaluate the contribution of protein biomarkers associated with early precancerous changes and tumor-initiating potential to subsequent risk of breast cancer among a large population-based cohort. Almost 15,000 women who received benign breast biopsies since 1996 were followed for breast cancer until 2009 by the New Mexico Tumor Registry, an NCI-sponsored SEER (Surveillance, Epidemiology, End Results) site that has been gathering information on cancer in New Mexico since 1968. A nested case-control study was conducted, and women who developed breast cancer were matched to three controls. An initial 85 breast cancer cases and 245 controls were evaluated for expression of 20 protein biomarkers in their benign biopsy tissue using immunohistochemistry. Included biomarkers are known to be active in pathways contributing to the earliest events in carcinogenesis. Our goal in this proposal is to complete the pathologist scoring of the immunohistochemical staining, analyze the data, and submit them for publication. Our efforts will include optimization of novel methods to determine the simultaneous presence of several biomarkers, to facilitate such assessment in future epidemiologic studies. Our study can serve two important purposes: (1) To improve risk models to more precisely distinguish women who will (and will not) go on to breast cancer; and (2) To identify biomarkers of malignant potential that may serve as targets for development of new prevention initiatives. Our goal in this grant is to more precisely distinguish women at high risk of breast cancer at least several years before pathologic detection of the tumor, when prevention might reasonably deter or delay its' development, and to provide information on biomarker expression in specific cancer-related pathways, which might guide tailored prevention efforts.

描述（由申请人提供）：虽然美国一生中有很大一部分妇女在其一生中被视为“高风险”（Graubard 2010），但大多数人永远不会培养乳腺癌。被认为处于高风险的妇女面临着使癌症陷入困境的大多数困难选择。有些人有资格接受内分泌疗法，例如他莫昔芬或雷昔芬，这些疗法与某些用户的严重副作用有关。高风险女性的预防选择受到限制，部分原因是我们对引起乳腺癌的生物学因素的理解是相当基本的。此外，我们当前的风险模型仅估计随后的癌症，并且由于有效且可接受的预防选择是稀缺的，因此大多数处于较高风险的妇女被确定为较高的妇女，或提供降低疗法的风险。因此，有鉴定与随后风险有关的乳腺组织中的生物标志物的迫切需要，这可能有助于改善对高风险的妇女的识别，并迅速开发针对其乳房组织变化的疗法。我们建议评估与早期癌前变化和肿瘤发射潜力相关的蛋白质生物标志物在大型基于人群的同类群中患乳腺癌风险的潜力。自1996年以来，近15,000名接受了良性乳腺活检的妇女一直受到乳腺癌的追踪，直到2009年由新墨西哥州肿瘤注册表（New Mexico Tumor Registry）是NCI赞助的SEER（监视，流行病学，最终结果）网站，自1968年以来一直在新墨西哥收集有关癌症的信息，自1968年以来一直在新墨西哥州进行癌症。进行了病例对照研究，并进行了乳腺癌的乳腺癌，并与之相配。使用免疫组织化学评估了最初的85例乳腺癌病例和245例对照在其良性活检组织中表达20种蛋白质生物标志物。已知包含的生物标志物在造成癌变最早事件的途径中活跃。我们在这项建议中的目标是完成免疫组织化学染色的病理学家评分，分析数据并提交出版。我们的努力将包括优化新方法来确定几种生物标志物的同时存在，以促进未来的流行病学研究中的这种评估。我们的研究可以实现两个重要目的：（1）改善风险模型，以更精确地区分那些将（也不会）继续进行乳腺癌的女性；（2）确定可能是发展新预防计划的目标的恶性潜力的生物标志物。我们在这笔赠款中的目标是至少在病理检测前几年，在预防可能合理地阻止或延迟其发展的情况下，更精确地区分乳腺癌高风险的妇女，并提供有关特定癌症相关途径中生物标志物表达的信息，这可能指导量身定制的预防措施。