Molecular detection of breast cancer in peripheral blood

目前乳腺癌的分期方法都是侵袭性的，费用昂贵，缺乏敏感性。最近乳腺癌中高表达基因的发现和分子生物学的进展为灵敏地检测外周血中乳腺癌的分子诊断方法的发展提供了动力。候选人威廉·E·吉兰德斯医学博士，是南卡罗来纳医科大学(MUSC)的外科助理教授，立志成为一名独立的内科科学家。他在基础科学方面有着深厚的背景，并在这一应用中展示了实时RT-PCR允许对基因表达进行灵敏检测和量化，以及磁性细胞浓缩技术可用于从外周血中分离乳腺癌细胞的初步数据。这两项技术的成功结合为乳腺癌分期提供了革命性的机会。这项研究的假设是，实时RT-PCR检测乳腺癌患者外周血中的乳腺癌细胞与临床结果相关。具体目标1的实验将建立方案，并确定实时RT-PCR检测外周血中乳腺癌细胞的灵敏度。将严格评估密度分离介质和磁性细胞浓缩技术。一项针对特定目标2的先导性临床研究将证实已建立的方案在IV期乳腺癌患者中的可行性和临床相关性。在特定目的3中，建议使用乳腺癌微创分子分期试验(MIMS)的外周血液样本进行相关研究。在MUSC有许多资源来促进候选人的研究和职业发展。其中包括霍林斯癌症中心最先进的临床和研究设施，包括外科分子肿瘤学实验室和多学科乳腺癌诊所；NIH K30临床研究课程奖，支持MUSC的多学科临床研究培训计划；以及MIMS试验，提供临床试验管理和患者样本获取方面的候选经验。

The current staging modalities for breast cancer are invasive, expensive, and lack sensitivity. The recent identification of genes over-expressed in breast cancer combined with advances in molecular biology provide the impetus for the development of molecular diagnostic assays to sensitively detect breast cancer in peripheral blood. The candidate, William E. Gillanders, M.D., is an Assistant Professor of Surgery at the Medical University of South Carolina (MUSC) aspiring to become an independent physician scientist. He has a strong background in basic science, and presents preliminary data in this application that real-time RT-PCR allows for the sensitive detection and quantitation of gene expression, and that magnetic cell enrichment technologies can be used to isolate breast cancer cells from peripheral blood. The successful combination of these two technologies provides the opportunity to revolutionize breast cancer staging. The hypothesis of the proposed research is that real-time RT-PCR detection of breast cancer cells in the peripheral blood of breast cancer patients is associated with clinical outcome. Experiments in Specific Aim 1 will establish the protocol and define the sensitivity of real-time RT-PCR detection of breast cancer cells in peripheral blood. Density separation media and magnetic cell enrichment technologies will be rigorously evaluated. A pilot clinical study in Specific Aim 2 will confirm the feasibility and clinical relevance of the established protocol in Stage IV breast cancer patients. A correlative study is proposed in Specific Aim 3 using peripheral blood specimens from the Minimally Invasive Molecular Staging of Breast Cancer Trial (MIMS). There are a number of resources at MUSC to facilitate the candidate's research and career development. These include state-of-the-art clinical and research facilities in the Hollings Cancer Center including the Surgical Molecular Oncology Laboratory, and the Multidisciplinary Breast Cancer Clinic; and NIH K30 Clinical Research Curriculum Award supporting a multi-disciplinary clinical research training program at MUSC; and the MIMS Trial providing the candidate experience in clinical trials management and access to patient samples.