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：
8176348
负责人：
SAMIR M HANASH
金额：
$ 22.97万
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/8176348
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. PUBLIC HEALTH RELEVANCE: There is a substantial need to identify women at increased risk for developing breast cancer. Prior studies by the applicants using in-depth quantitative technology to profile circulating proteins in the blood for potential risk markers have identified many potential markers of risk among post-menopausal women that subsequently developed breast cancer. These novel candidate risk markers for breast cancer require additional studies for their verification. The objectives of this proposal to do additional verification studies of the candidate biomarkers in an independent set of women from the Women's Health Initiative and to determine the relevance of these markers as mediators of the risk for breast cancer associated with post-menopausal hormone therapy.

描述（由申请人提供）：肯定需要确定乳腺癌风险的生物标志物。深入的定量蛋白质组学方法应用于对乳腺癌诊断之前收集的等离子体分析，以寻找这种疾病的候选候选标志。样品是从妇女健康倡议（WHI）队列中获得的，由在收集血液的七年内被诊断出患有乳腺癌的妇女组成，对年龄，自我报告的种族，子宫切除术和入学日期匹配的对照组成。在平行研究中，将蛋白质组学分析应用于基线在基线和一年后用共轭马雌激素（CEE）或CEE/MPA（Medroxyprogestretelone乙酸）获得的血液样本。广泛的蛋白质组学分析确定了受HRT影响的大量循环蛋白，还产生了一组值得额外验证研究的乳腺癌风险标志物候选者。有趣的是，一些候选者也受到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AIM 1中，我们建议对使用来自WHI激素治疗试验的独立参与者识别的风险标记进行确认研究，该试验患有乳腺癌并匹配对照。在接受确认研究的14名候选人中，有8个具有ELISA，可以进行测定。其余的候选者将使用多个反应监测质谱法进行确认。第二个目标包括评估确定的风险标志物作为激素治疗对乳腺癌的影响。为此，将利用在基线和CEE/MPA试验中收集的等离子体，并在CEE/MPA试验中确定案例和匹配对照中风险标志物候选物浓度的变化。拟议的项目有可能贡献与临床相关的乳腺癌生物标志物，以识别有风险增加的女性，并阐明与绝经后激素治疗相关的乳腺癌风险。公共卫生相关性：确定患乳腺癌风险增加的妇女迫切需要。使用深入定量技术的申请人的先前研究对血液中的循环蛋白进行了潜在的风险标志物的循环蛋白质，从而确定了后来妇女的许多潜在风险标志，随后患上了乳腺癌。这些新型候选乳腺癌的候选风险标记需要进行核心验证。该提案的目标是对妇女健康计划中独立妇女的候选生物标志物进行额外验证研究，并确定这些标志物作为与绝经后激素治疗相关的乳腺癌风险的介体的相关性。