Developing Biomarker-Based Prognostics In Breast Cancer

开发基于生物标志物的乳腺癌预后

• 批准号: 6761233
• 负责人: JOHN A. OLSON
• 金额: $ 13.1万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-06 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6761233
• 关键词: biomarker; breast neoplasms; clinical research; disease /disorder model; female; gene expression; hormone receptor; human subject; lymph nodes; metastasis; microarray technology; model design /development; neoplasm /cancer classification /staging; neoplasm /cancer relapse /recurrence; patient oriented research; postmenopause; prognosis; western blottings; women' s health

DESCRIPTION (provided by applicant): The candidate's objective is to build upon his background in clinical surgical oncology and human molecular genetics to become a leader in the translation of new genome technologies to the care of patients with breast cancer. Through the steps outlined current proposal the candidate will obtain necessary additional expertise in 1) genome science, 2) bioinformatics and statistics, and 3) clinical trial design to improve biomarker based prognostic models and validate them in prospective clinical trials. The candidate is well positioned in a committed group of senior investigators in genomics and bioinformatics who have made significant recent contributions in this field. His clinical expertise in breast oncology, his unique perspective on tissue acquisition for biomarker studies, and his unique access to correlative science development and clinical trials through the American College of Surgeons Oncology Group affords him the unique opportunity to bridge the gap between development of new knowledge and its validation in clinical trials. The candidate and his mentors have constructed a program of scientific development and investigation centered around testing the hypothesis that ascertainment of biologic variability in gene expression as well as incorporating protein biomarker expression to gene expression-based predictive models will improve the ability of these models to predict breast cancer outcomes, including metastasis to axillary lymph nodes and disease recurrence. Specifically, the aims are: Specific Aim 1: To measure variability in gene expression in TIN0M0 hormone receptor positive breast cancer in pre- and postmenopausal women and ascertain whether this variability changes expression-based model predictions of axillary metastasis and recurrence from breast cancer. Specific Aim 2: To determine whether enhanced pathologic staging of axillary lymph node status improves the accuracy of gene expression-based predictive models. Specific Aim 3: To determine whether incorporating protein biomarker data into a gene expression-based predictive tree model improves the predictive accuracy of the model Specific Aim 4: To prospectively test a gene expression and protein biomarker-based predictive tree model in a multi-institutional pilot study.

描述(申请人提供)：候选人的目标是在他的临床外科肿瘤学和人类分子遗传学背景的基础上，成为将新的基因组技术转化为乳腺癌患者护理的领导者。通过目前提议的步骤，候选人将在1)基因组科学，2)生物信息学和统计学，以及3)临床试验设计方面获得必要的额外专业知识，以改进基于生物标记物的预后模型，并在预期的临床试验中验证它们。这位候选人在致力于基因组学和生物信息学的高级研究人员团队中处于有利地位，他们最近在这一领域做出了重大贡献。他在乳腺肿瘤学方面的临床专业知识、他在用于生物标记物研究的组织获取方面的独特视角，以及他通过美国外科医师学院肿瘤学小组获得相关科学发展和临床试验的独特机会，为他提供了弥合新知识开发与临床试验验证之间差距的独特机会。这位候选人和他的导师们构建了一个科学发展和调查计划，以测试以下假设为中心：确定基因表达的生物变异性，以及将蛋白质生物标记物的表达纳入基于基因表达的预测模型，将提高这些模型预测乳腺癌结果的能力，包括腋窝淋巴结转移和疾病复发。具体来说，目标是： 具体目标1：测量绝经前和绝经后TIN0M0激素受体阳性乳腺癌中基因表达的变异性，并确定这种变异性是否改变了乳腺癌腋窝转移和复发的基于表达的模型预测。 具体目标2：确定腋窝淋巴结状态的增强病理分期是否提高了基于基因表达的预测模型的准确性。 具体目标3：确定将蛋白质生物标记物数据纳入基于基因表达的预测树模型是否提高了模型的预测精度 具体目标4：在一项多机构的先导研究中，前瞻性地测试基于基因表达和蛋白质生物标记物的预测树模型。