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.
|Baker, Megan K; Mikhitarian, Kaidi; Osta, Walid et al. (2003) Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin Cancer Res 9:4865-71|