Breast Pre-Cancer Atlas Center

乳腺癌前期阿特拉斯中心

• 批准号: 10732796
• 负责人: E.Shelley Hwang
• 金额: $ 16.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10732796
• 关键词: 3-Dimensional; Address; Anxiety; Atlases; Bilateral; Biological Assay; Breast; Cells; Characteristics; Chemotherapy and/or radiation; Clinical; Clinical Trials; Communities; Confusion; Consensus; Data; Data Storage and Retrieval; Detection; Development; Diagnosis; Dimensions; Disease; Disease Management; Distress; Duct (organ) structure; Ecology; Elements; Evolution; FAIR principles; Future; Gene Expression; Histologic; Image; Inflammatory; Informatics; Intervention; Investigation; Life; Longitudinal Studies; Malignant Neoplasms; Mammography; Mastectomy; Measures; Methodology; Methylation; Modeling; Molecular; Morbidity - disease rate; Mutation; Natural History; Noninfiltrating Intraductal Carcinoma; Operative Surgical Procedures; Outcome; Pathologic; Pathway interactions; Patient Care; Patient observation; Patients; Phase; Premalignant Cell; Provider; Quality of life; Radiology Specialty; Research Personnel; Resources; Risk; Sampling; Solid Neoplasm; Sum; Testing; Tissues; Toxic effect; United States; Woman; Work; breast lumpectomy; calcification; cancer invasiveness; clinical diagnosis; cohort; data visualization; design; disease natural history; evidence base; experience; flexibility; improved; knowledge of results; malignant breast neoplasm; member; multimodal data; multimodality; next generation; novel; premalignant; prevent; progression risk; prospective; risk stratification; screening; statistics; tool; tumor

ABSTRACT – Overall Development of invasive breast cancer may frequently progress through a preinvasive precursor called ductal carcinoma in situ (DCIS). DCIS is an extremely common clinical diagnosis that is essentially a disease of screening triggered by the detection of abnormal breast calcifications on mammography. Before the advent of mammography, DCIS was an incidental and relatively uncommon finding. Over 60,000 women in the United States will be presented with this diagnosis each year with relatively weak evidence-based guidance for disease management which ranges from active surveillance to bilateral mastectomy. We propose to compile multi-dimensional and multi-scale information on DCIS to construct a Pre-Cancer Atlas that can be used to better understand the disease but also to better stratify risk of progression, a useful translational endpoint. To do this, we have assembled a team of investigators with deep and complementary clinical, experimental, and quantitative expertise and experience with DCIS and breast cancer in general. Further, we conduct these studies with full consideration of tumor evolution and ecology as it pertains to precancer development and progression. Specific aspects of the proposed Atlas construction include: 1) Several types of DCIS cohorts that will capture spatial and longitudinal information including a prospective clinical trial cohort undergoing active surveillance, 2) Analyses designed to maintain relevant spatial organization of the disease for evolutionary and Atlas building considerations based on 3) Radiologic-histologic-cellular-molecular registration approaches, 4) Characterization at multiple scales including whole tumor, single duct and single cell levels, 5) Characterization of relevant parameters including mutations, copy number changes, methylation, gene expression, and microenvironmental elements including inflammatory cell profiles. 6) Incorporation of the breast cancer intrinsic subtype paradigm into the analytic phase, and 7) Layered, spatial, and longitudinal data visualization. Overall, this work will provide a comprehensive platform to guide the next generation of studies on DCIS and other precancers.

摘要--总体 浸润性乳腺癌的发展可能经常通过一种称为导管的侵袭前驱物进展。 原位癌(DCIS)。DCIS是一种非常常见的临床诊断，本质上是一种疾病 在乳房X光检查中发现异常的乳房钙化而触发的筛查。在……出现之前 乳房X光检查显示，DCIS是一种偶然且相对罕见的发现。美国有超过6万名女性 每年将向各州提交这一诊断，对以下方面的循证指导相对薄弱 疾病管理，从积极监测到双侧乳房切除术。我们建议编制一份 多维多尺度DCIS信息构建癌前地图集 更好地了解这种疾病，还可以更好地对进展风险进行分层，这是一个有用的翻译终点。至 为此，我们组建了一支研究团队，具有深入和互补的临床、实验和 在DCIS和乳腺癌方面的定量专业知识和经验。此外，我们还进行了这些 充分考虑肿瘤进化和生态学的研究，因为它与癌症前发展和 进步。拟议的Atlas建设的具体方面包括：1)几种类型的DCIS队列 将捕获空间和纵向信息，包括正在进行的预期临床试验队列 监测，2)旨在维持疾病的相关空间组织的分析，以供进化和 基于3)放射学-组织学-细胞-分子配准方法的图集构建考虑，4) 包括整个肿瘤、单管和单细胞水平的多尺度特征，5)特征 相关参数包括突变、拷贝数变化、甲基化、基因表达和 微环境因素，包括炎性细胞图谱。6)合并固有的乳腺癌 子类型范例进入分析阶段，以及7)分层、空间和纵向数据可视化。总的来说， 这项工作将提供一个全面的平台，指导下一代关于DCIS和其他 癌症前期。