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

• 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
• 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' 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

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）：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，蛋白质组分析应用于基线时和一年结合马雌激素 (CEE) 或 CEE/MPA（醋酸甲羟孕酮）激素治疗 (HT) 后获得的血液样本。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 年收集的血浆来确定病例和匹配对照中候选风险标记物浓度的变化。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，并澄清与绝经后激素治疗相关的乳腺癌风险。 公共卫生相关性：非常需要确定罹患乳腺癌风险较高的女性。申请人之前的研究使用深入的定量技术来分析血液中的循环蛋白以寻找潜在的风险标记，已经在随后患乳腺癌的绝经后妇女中识别出许多潜在的风险标记。这些新的乳腺癌候选风险标志物需要额外的研究来验证。该提案的目标是对来自妇女健康倡议的一组独立女性的候选生物标志物进行额外的验证研究，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中介的相关性。