Core - Biomarker Developmental Laboratory (BDL)

项目摘要/摘要(生物标志物开发实验室(BDL)部分，RFA-CA-22-040) 我们建议开发一种基于血液的测试，其指定用途是补充早期的乳房X光检查。 乳腺癌的检测。虽然乳房X光检查通过早期发现拯救了生命，但它并不完美。 大约七分之一的乳腺癌在筛查乳房X光检查后仍未被发现，而且间隔时间 在正常乳房X光检查后一年内出现的癌症仍然是一个令人头疼的问题，尤其是(尽管不是 独家)针对美国2700万拥有异质或极致密乳房的女性 间歇性癌症的高风险。我们建议开发一种血液测试，可以作为辅助手段 乳房X光检查通过提高乳房X光检查的敏感度和/或特异度来改进早期检测。 使用一种新的生物标记物发现方法，利用人在小鼠体内的乳腺癌患者来源 异种移植模型和最先进的质谱学方法，我们优先考虑162个候选对象的子集 用于随访的乳腺癌蛋白生物标记物(在乳腺癌患者与对照的人血浆中得到验证) EDRN第二阶段验证研究在这一建议的BCC。 我们的项目将在临床上验证和部署(在我们的CLIA实验室)一种新的多重免疫多种多样 反应监测质谱仪检测EDRN 2期生物标志物 使用从现有生物信息库获得的强无偏血浆样本集进行验证研究。 生物标记物开发实验室将为拟议的EDRN第二阶段生物标记物验证做出贡献 研究人员：(I)遵循基于临床和实验室标准协会(CLSI)文件的行业指南 C64为162个早期候选蛋白质生物标志物开发合格试剂和方法 乳腺癌，(Ii)采购血浆生物样品(使用EDRN探针研究设计收集，以避免偏见) 对于EDRN阶段2生物标记物验证研究，(Iii)将血浆等量盲法提供给我们的BRL CLIA实验室 以及(Iv)分析由BRL生成的EDRN阶段2验证数据，提供统计， 流行病学和乳房成像专业知识，以设置和评估性能指标，以确保生物标志物 足以为早期发现提供临床实用价值。

Project Summary/Abstract (Biomarker Development Laboratory (BDL) Component, RFA-CA-22-040) We propose to develop a blood-based test whose indicated use is to complement mammography in the early detection of breast cancers. Although mammography saves lives through early detection, it is imperfect. Approximately one in seven breast cancers goes undetected despite screening mammography, and interval cancers that manifest within a year of a normal mammogram remain a vexing problem, especially (although not exclusively) for the >27 million women in the United States with heterogeneously or extremely dense breasts at high risk for interval cancers. We propose to develop a blood test that could be used as an adjunct to mammography to improve early detection by improving sensitivity and/or specificity of mammography. Using a novel biomarker discovery approach leveraging human-in-mouse breast cancer patient-derived xenograft models and state-of-the-art mass spectrometry methods, we prioritized a subset of 162 candidate breast cancer protein biomarkers (verified in human plasma from breast cancer cases vs. controls) for follow up EDRN phase 2 validation studies in this proposed BCC. Our project will clinically validate and deploy (in our CLIA laboratories) a novel multiplex immuno-multiple reaction monitoring mass spectrometry (immuno-MRM-MS) assay to perform EDRN phase 2 biomarker validation studies using strongly unbiased sets of plasma samples obtained from existing biorepositories. The Biomarker Development Laboratory will contribute to the proposed EDRN phase 2 biomarker validation studies by: (i) following industry guidelines based on Clinical and Laboratory Standards Institute (CLSI) document C64 to develop qualified reagents and methods for quantifying 162 candidate protein biomarkers of early-stage breast cancer, (ii) procuring plasma biospecimens (collected using the EDRN PRoBE study design to avoid bias) for EDRN phase 2 biomarker validation studies, (iii) delivering plasma aliquots to our BRL CLIA labs in a blinded fashion, and (iv) analyzing EDRN phase 2 validation data generated by the BRL, providing statistical, epidemiological, and breast imaging expertise to set and evaluate performance metrics to ensure biomarkers are adequate to provide clinical utility for early detection.