Multimarker miR Blood Assay for Breast Cancer Detection

Current approaches of breast cancer screening by mammograms, ultrasound, and tissue core biopsy are costly and inefficient. Breast cancer detection with a blood assay would be less costly, more efficient, and more logistically practical to routinely screen women in the community. MicroRNAs (miRs) represent a class of naturally occurring small non-coding RNA molecules (18~22 nucleotides). Some miRs are expressed in a tissue-specific manner and are considered to play pivotal functional roles. Studies have demonstrated expression of various miRs in various human cancers, including breast cancer indicating that they may be potential biomarkers. Although circulating nucleic acids (DNA and mRNA) have clinical utility in cancer patients, their assessment of in serum/plasma specimens has been problematic because of nucleic acid instability and degradation which compromise overall assay sensitivity. By contrast, miRs are highly stable in serum and therefore suitable for investigation as ideal serum biomarkers. Traditional blood protein biomarkers have not been sensitive enough to detect early stage breast cancer. However, isolation of sufficient amounts of small nucleic acids, such as miR, for biomarker evaluation is extremely difficult. We recently developed a direct qRT-PCR (quantitative real-time PCR) assay for investigating circulating miR in order to bypass miR loss during extraction. One specific miR, called miR-21 is up-regulated in human breast cancer tissue. This project will determine if circulating miR-21 and other miRs in serum could be used to detect early-stage breast cancer with greater sensitivity and accuracy than standard screening/detection. Our overall objective is to develop a multi-marker miR biomarker panel. Our specific aims are: 1. Develop a robust direct serum assay to detect miR breast biomarkers in early-stage breast cancer patients. 2. Assess the utility of multi-marker miR breast biomarkers and compare their efficiency and accuracy in breast cancer detection to that of mammography, ultrasound, and tissue core biopsy. 3. Determine the clinical utility of the multi-marker serum miR breast biomarker assay for detection of disease recurrence in node-negative early-stage breast cancer patients. The miR assay will require The success of multi-marker serum miR biomarker could potentially reduce health care costs, improve screening for breast cancer detection, follow-up for recurrence, reduce exposure from radiation of repetitive imaging approaches, and allow for greater screening compliance.