Breast and Ovary Cancer Clinical Validation Center

描述（由申请人提供）：在过去的几年里，我们的多学科研究团队一直致力于发现和验证乳腺癌和卵巢癌的候选早期检测生物标志物。我们现在处于领导EDRN CVC的理想位置，原因有几个：1.我们有一系列有前景的乳腺癌和卵巢癌早期检测生物标志物，这些生物标志物已在1期至3期早期验证研究中进行了评估，这些研究需要在3期研究中进行进一步研究; 2.我们在癌症生物标志物发现和验证研究的设计、实施、分析和解释方面积累了相当多的专业知识; 3.在四项工作的过程中，我们已经开发或获得了大量高质量的、特征良好的乳腺癌和卵巢癌样本库，我们愿意与EDRN分享; 4.我们在领导和支持涉及共享样本的合作项目方面有着悠久的历史，我们制定了程序来促进样本请求的处理和跟踪。在此，我们提出了一个新的前瞻性收集乳腺癌病例和对照的临床前标本，这是独一无二的，因为它将包括详细的乳房X线摄影信息。我们还提出了一系列主要的3期验证研究。对于乳腺癌，我们将在第1年（研究1）开始进行3期研究，然后计划在第4-5年（研究5）设计一系列2期和3期研究，因为我们的工作和EDRN的其他候选人成熟。研究1的主要具体目标是使用临床前样本对大型发现项目中确定的有希望的候选人进行第二次筛选，然后在WHI的一组独立的临床前样本中验证最佳候选人。对于卵巢癌，我们建议在第1-3年进行一系列连续的3项3期研究。已经验证了几种卵巢癌生物标志物，但没有一种能够单独实现临床有用的性能。因此，研究2是一项3期验证，旨在使用PLCO试验的系列临床前样本验证和改进两个和四个标记算法。研究3将进一步验证UKCTOCS试验临床前系列样本中的特定筛选决策规则。基于研究2和3，研究4将在一组独立的WHI系列临床前样本中验证卵巢癌标志物和筛选决策规则，在该设置中未进行卵巢癌筛选。

DESCRIPTION (provided by applicant): Over the past several years our multidisciplinary research team has been dedicated to discovering and validating candidate early detection biomarkers for breast and ovary cancers. We are now in an ideal position to lead an EDRN CVC for several reasons: 1. We have lists of promising breast and ovary cancer early detection biomarkers that have been evaluated in Phase 1 to early Phase 3 validation studies that warrant further investigation in Phase 3 studies; 2. We have developed considerable expertise in the design, conduct, analysis, and interpretation of cancer biomarker discovery and validation studies; 3. Over the course of four work we have developed or gained access to a large number of high quality well-characterized breast and ovary cancer sample repositories that we are willing to share with EDRN; and 4. We have a long history of leading and supporting collaborative projects that have involved shared samples, and we have procedures in place to facilitate the processing and tracking of specimen requests. Herein we propose a new prospective collection of preclinical specimens from breast cancer cases and controls which is unique in that it will include detailed mammography information. We also propose a series of primarily Phase 3 validation studies. For breast cancer we will conduct a Phase 3 study beginning in Year 1 (Study 1) and then plan to design a series of Phase 2 and 3 studies in Years 4-5 (Study 5) as candidates from our work and others in EDRN mature. The primary specific aim of Study 1 is to conduct a second screen of promising candidates identified in a large discovery project using preclinical samples, and to then validate the top candidates in an independent set of preclinical samples from WHI. For ovary cancer we propose a consecutive series of three Phase 3 studies over Years 1-3. Several ovary cancer biomarkers have been validated, but none achieve clinically useful performance on their own. Thus, Study 2 is a Phase 3 validation aimed at validating and refining two- and four-marker algorithms using serial preclinical samples from the PLCO trial. Study 3 will further validate specific screening decision rules in preclinical serial samples from the UKCTOCS trial. Based on Studies 2 and 3, Study 4 will validate ovary cancer markers and screening decision rules in an independent set of WHI serial preclinical samples, a setting in which no ovary cancer screening occurred.