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）：虽然美国很大一部分女性被认为在其一生中处于患乳腺癌的“高风险”（Graubard 2010），但大多数女性永远不会患乳腺癌。被认为处于高风险的女性在预防癌症方面面临着大多数艰难的选择。有些人适合接受内分泌疗法，例如他莫昔芬或雷洛昔芬，这些疗法对某些使用者来说会产生严重的副作用。高风险女性的预防选择有限，部分原因是我们对导致乳腺癌的生物因素的了解相当初级。此外，我们当前的风险模型只能不精确地估计风险由于有效和可接受的预防方案很少，大多数高风险女性没有被识别出来，也没有得到降低风险的治疗。因此，有迫切需要确定乳腺组织中与后续风险相关的生物标志物，这可能有助于更好地识别高风险女性，并促进针对其乳腺组织变化的治疗方法的开发。我们建议在基于人群的大型队列中评估与早期癌前变化和肿瘤引发潜力相关的蛋白质生物标志物对随后乳腺癌风险的贡献。新墨西哥州肿瘤登记处自 1996 年以来对近 15,000 名接受良性乳腺活检的女性进行了乳腺癌随访，直至 2009 年。新墨西哥州肿瘤登记处是一个由 NCI 资助的 SEER（监测、流行病学、最终结果）网站，自 1968 年以来一直在收集新墨西哥州的癌症信息进行了一项巢式病例对照研究，将患乳腺癌的女性与三名对照者进行匹配。使用免疫组织化学评估了最初的 85 名乳腺癌病例和 245 名对照者的良性活检组织中 20 种蛋白质生物标志物的表达。已知所包含的生物标志物在促成癌发生最早事件的途径中具有活性。我们本提案的目标是完成免疫组织化学染色的病理学家评分、分析数据并提交发表。我们的努力将包括优化新方法来确定多种生物标志物的同时存在，以促进未来流行病学研究中的此类评估。我们的研究可以达到两个重要目的：（1）改进风险模型，以更准确地区分将（和不会）患乳腺癌的女性； (2) 确定具有恶性潜力的生物标志物，可以作为制定新预防措施的目标。我们这笔赠款的目标是在肿瘤病理检测前至少几年更准确地区分乳腺癌高风险女性，此时预防可能合理阻止或延迟其发展，并提供有关特定癌症中生物标志物表达的信息。相关途径，这可能会指导有针对性的预防工作。