Developing Biomarker-Based Prognostics In Breast Cancer

描述（由申请人提供）：候选人的目标是建立在他在临床外科肿瘤学和人类分子遗传学方面的背景，成为将新的基因组技术转化为乳腺癌患者护理的领导者。通过当前提案概述的步骤，候选人将获得必要的额外专业知识：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，以改进基于生物标志物的预后模型，并在前瞻性临床试验中验证它们。该候选人是基因组学和生物信息学领域的资深研究人员，他们最近在该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，他对生物标志物研究组织获取的独特视角，以及他通过美国外科医师学会肿瘤学小组获得相关科学发展和临床试验的独特途径，为他提供了弥合新知识发展与临床试验验证之间差距的独特机会。该候选人和他的导师已经建立了一个科学发展和研究项目，其核心是验证一个假设，即确定基因表达的生物学变异性以及将蛋白质生物标志物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预后的能力，包括腋窝淋巴结转移和疾病复发。具体而言，目标是：

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.