Vermont Breast Cancer Molecular Characterization Laboratory

佛蒙特州乳腺癌分子表征实验室

基本信息

批准号：
9142299
负责人：
Brian L Sprague
金额：
$ 81.29万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-09 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9142299
关键词：
Address Adoption Advisory Committees Age Archives Behavior Breast Breast Cancer Detection Breast Cancer Surveillance Consortium Breast Cancer Treatment Breast Epithelial Cells Cancer Biology Cancer Center Cells Characteristics Collaborations Collection Complement Consensus Critiques Data Data Collection Development Diagnosis Disease Duct (organ) structure Epidemiology Exhibits Formalin Gene Expression Gene Expression Profile Genetic Transcription Goals Guidelines Indolent Interdisciplinary Study Journals Laboratories Lead Leadership Lesion Life Link Malignant - descriptor Malignant Neoplasms Mammary Gland Parenchyma Mammography Medical Medicine Methods Molecular Molecular Profiling New England New York Newly Diagnosed Noninfiltrating Intraductal Carcinoma Organ Outcome Paraffin Embedding Pathology Patients Play Population Preventive service Primary Neoplasm Procedures Radiology Specialty Recommendation Regimen Registries Research Research Personnel Research Project Grants Resources Role Screening for cancer Signal Transduction Site Specimen Staging Symptoms System Technology Therapeutic Intervention Time Tissues Treatment outcome Vermont Woman Work base biobank breast cancer diagnosis breast imaging breast tumorigenesis cancer diagnosis cancer epidemiology cancer therapy case control clinical care design experience innovation malignant breast neoplasm member minimally invasive mortality neoplastic neoplastic cell novel novel marker novel strategies outcome forecast population based precision medicine programs prospective public health relevance repository screening treatment strategy tumor microenvironment tumor progression

项目摘要

DESCRIPTION (provided by applicant): Advances in breast cancer screening and treatment have reduced breast cancer mortality in the US over the past 30 years. However, the widespread adoption of screening mammography has been accompanied by dramatic increases in early stage breast cancer diagnoses that have not been offset by declines in advanced stage disease. Accumulating evidence suggests that a substantial fraction of screen-detected breast cancers would never have emerged clinically if not detected through screening. While there is extensive debate regarding the magnitude of overdiagnosis, there is widespread consensus that new approaches are urgently needed to distinguish indolent screen-detected cases from those that may be life threatening. The role of the tumor microenvironment in breast cancer progression has been increasingly recognized. Several lines of evidence indicate that breast tumorigenesis is critically influenced by active signaling between malignant breast epithelial cells and non-neoplastic cells of the tumor microenvironment. The goal of our proposal is to identify tumor microenvironment signatures that predict the aggressiveness of early stage, screen-detected breast cancers by minimally invasive methods. We will leverage and refine state-of-the-art technologies to characterize aggressive signatures based on the cellular composition and gene expression of specific cell populations within the tumor microenvironment of interval- and symptom-detected invasive breast cancers. We will then determine whether the presence of these aggressive tumor microenvironment signatures in early stage, screen-detected breast cancer is associated with progression. We will obtain retrospective data on 800 formalin-fixed, paraffin-embedded specimens for analysis from the Vermont Breast Cancer Surveillance System (VBCSS), which has collected integrated patient, radiology, pathology, treatment, and outcomes data on all women undergoing breast imaging in the state of Vermont since 1996. The VBCSS has a large existing repository of over 1,200 centrally-reviewed DCIS specimens and access to over 10,000 invasive breast cancer specimens for cases diagnosed in the state of Vermont. We will also engage in prospective collection of fresh specimens via the Vermont Cancer Center Tissue Biobank, which is also linked to the integrated data of the VBCSS. The identification of aggressive and indolent tumor microenvironment signatures will promote the development of more conservative treatment strategies for the subset of women with favorable prognosis and suggest novel targets for therapeutic intervention in cases with unfavorable prognosis. We have assembled a multidisciplinary research team with nationally recognized expertise in cellular and molecular cancer biology, pathology, cancer screening, and epidemiology, as well as a long track record of productive consortium-based collaborative research. The Vermont Breast Cancer Molecular Characterization Laboratory will provide the consortium with scientific leadership, technical resources, and access to a large repository of retrospective and prospectively collected breast specimens linked to the rich data of the VBCSS.

描述（由适用提供）：在过去30年中，美国乳腺癌筛查和治疗的进展降低了乳腺癌的死亡率。然而，通过早期乳腺癌诊断的急剧增加，乳房X线摄影的宽度采用已经完成，而后期疾病的下降并未被晚期舞台疾病的下降所抵消。积累的证据表明，如果未通过筛查检测到很大一部分筛查的乳腺癌将永远不会在临床上出现。尽管关于过度诊断的幅度存在广泛的争论，但迫切需要新的方法与可能威胁生命的疾病的案例与可能威胁生命的案例区分开来，迫切需要新的方法来区分新方法。肿瘤微环境在乳腺癌进展中的作用已被识别出来。几条证据表明，乳腺肿瘤发生受到肿瘤微环境的恶性乳房上皮细胞和非肿瘤细胞之间的主动信号的严重影响。我们建议的目的是确定肿瘤微环境的特征，以通过微创方法预测早期，筛查乳腺癌的侵略性。我们将利用和完善最先进的技术来表征基于肿瘤微环境中特定细胞群体的细胞组成和基因表达的侵袭性特征，并探索了症状和症状探测的浸润性乳腺癌。然后，我们将确定这些侵略性肿瘤微环境在早期是否存在，筛查乳腺癌与进展有关。我们将获得800个福尔蒙固定的，石蜡包裹的标本的回顾性数据，以分析佛蒙特州乳腺癌监视系统（VBCSS），该系统已收集了综合的患者，放射学，病理学，治疗，并在1996年以来均经过一份乳房的乳房成像。 DCIS物种和佛蒙特州诊断的病例获得了10,000多种侵入性乳腺癌物种。我们还将通过Vermont Cancer Center Tissue Biobank进行前瞻性收集新鲜物种，这也与VBCSS的综合数据有关。鉴定侵略性和懒惰的肿瘤微环境特征将促进为具有良好预后的女性子集的子集的更保守的治疗策略的发展，并在预后不利的情况下提出了治疗干预的新颖靶标。我们组建了一个多学科研究团队，具有全国认可的细胞和分子癌生物学，病理学，癌症筛查和流行病学方面的专业知识，以及基于产品财团的协作研究的长期记录。佛蒙特州乳腺癌分子特征实验室将为该财团提供科学领导，技术资源，并获得与VBCSS丰富数据相关的回顾性和前瞻性收集的乳房标本的大量存储库。