CONFIRMATION STUDIES OF BLOOD BASED BIOMARKERS OF RISK FOR BREAST CANCER

乳腺癌风险的血液生物标志物的确认研究

基本信息

批准号：
8290296
负责人：
SAMIR M HANASH
金额：
$ 19.14万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8290296
关键词：
Address Affect Age Biological Assay Biological Markers Blood Blood specimen Collection Conjugated Equine Estrogens Diagnosis Diagnostic Disease Enrollment Ethnic Origin Evaluation Hysterectomy Intervention Mass Spectrum Analysis Mediator of activation protein Medroxyprogesterone 17-Acetate Participant Pathway interactions Patient Self-Report Phase Plasma Plasma Proteins Post-Menopausal Hormone Replacement Therapy Postmenopause Proteins Proteomics Randomized Randomized Controlled Trials Recording of previous events Relative (related person)Risk Risk Marker Sampling Specimen Technology Testing Uterus Visit Woman Women&apos s Health base breast cancer diagnosis cancer risk candidate marker case control clinically relevant cohort disorder risk follow-up hormone therapy malignant breast neoplasm multiple reaction monitoring novel validation studies

项目摘要

DESCRIPTION (provided by applicant): There is a substantial need to identify biomarkers of risk for breast cancer. An in-depth quantitative proteomics approach was applied to the analysis of plasmas that were collected prior to a diagnosis of breast cancer in search for candidate markers of risk for this disease. The samples were obtained from the Women's Health Initiative (WHI) cohort and consisted of women diagnosed with breast cancer within seven years of blood collection and controls matched for age, self-reported ethnicity, hysterectomy status and enrollment date. In parallel studies proteomic profiling was applied to blood specimens obtained at baseline and following one year of hormone therapy (HT) with conjugated equine estrogen (CEE) or CEE/MPA (medroxyprogesterone acetate). Extensive proteomic analyses identified a large subset of circulating proteins that were affected by HRT, and has also yielded a set of breast cancer risk marker candidates that merit additional validation studies. Interestingly some of the risk candidates were also affected by HRT and thus may contribute to elucidation of breast cancer risk associated with CEE/MPA therapy. In aim 1, we propose to conduct a confirmation study of risk markers identified using an independent set of WHI participants from the WHI hormone therapy trials who developed breast cancer and matched controls. Of the 14 candidates to be subjected to confirmation studies, eight have ELISAs available that would allow their assay. The remainder of the candidates would be subjected to confirmation using Multiple Reaction Monitoring mass spectrometry. A second aim consists of evaluating the identified risk markers as mediators of hormone therapy effects on breast cancer. To that effect plasmas collected at baseline and at 1-year of HT in the CEE and CEE/MPA trials will be utilized to determine changes in concentration of risk marker candidates in cases and in matched controls. The proposed project has the potential to contribute clinically relevant breast cancer biomarkers to identify women at increased risk and to clarify breast cancer risk associated with postmenopausal hormone therapy.

描述（由申请人提供）：非常需要鉴定乳腺癌风险的生物标志物。应用深入的定量蛋白质组学方法来分析在诊断乳腺癌之前收集的血浆，以寻找该疾病风险的候选标记。这些样本取自妇女健康倡议 (WHI) 队列，由采血后七年内诊断出患有乳腺癌的女性和年龄、自我报告的种族、子宫切除状况和入组日期相匹配的对照组成。在平行研究中，对基线时和使用结合马雌激素 (CEE) 或 CEE/MPA（醋酸甲羟孕酮）进行激素治疗 (HT) 一年后获得的血液样本进行了蛋白质组分析。广泛的蛋白质组学分析确定了受 HRT 影响的大量循环蛋白质，并且还产生了一组值得进行额外验证研究的乳腺癌风险标记候选物。有趣的是，一些候选风险也受到 HRT 的影响，因此可能有助于阐明与 CEE/MPA 治疗相关的乳腺癌风险。在目标 1 中，我们建议使用来自 WHI 激素治疗试验的一组独立的 WHI 参与者（患有乳腺癌和匹配对照）来对确定的风险标记进行确认研究。在接受确认研究的 14 名候选者中，有 8 名拥有可进行检测的 ELISA。其余候选者将使用多重反应监测质谱进行确认。第二个目标包括评估已确定的风险标志物作为激素治疗对乳腺癌影响的中介因素。为此，将利用 CEE 和 CEE/MPA 试验中基线和 HT 1 年时收集的血浆来确定病例和匹配对照中候选风险标志物浓度的变化。拟议的项目有可能提供临床相关的乳腺癌生物标志物，以识别风险增加的女性，并阐明与绝经后激素治疗相关的乳腺癌风险。