BIOM-60. ENRICHMENT OF CIRCULATING TUMOR CELLS EXPRESSING THE HER2 MARKER FROM CEREBRAL SPINAL FLUID USING THE CELLSEARCH® SYSTEM AND THE CELLSEARCH® CTC/HER2 LOW TEST FOR USE IN METASTATIC BREAST CANCER RELATED LEPTOMENINGEAL CARCINOMATOSIS

Abstract Up to 16% of patients with metastatic breast cancer (mBC) will develop brain metastasis during the natural history of their disease. Leptomeningeal carcinomatosis (LMC) involves dissemination of the cancer cell to the cerebral spinal fluid (CSF) and is a late, rare complication, which portends a poor prognosis. The current diagnostic “gold standard” for LMC is positive cytology testing with supporting evidence from central nervous system Magnetic Resonance Imaging (MRI). Neither approach measures the expression levels of key CSF markers in circulating tumor cells (CTCs), which has proven valuable for management decision-making. Liquid biopsy of blood has been used to detect CTCs and the HER2 marker processed on the Menarini Silicon Biosystems (MSB) CELLSEARCH® System using the CELLSEARCH® CTC/HER2 Low assay. To assess the value of the CTC-HER2 assay in measuring CTCs with HER2 expression in CSF, varying volumes, 5.0mls to 1.0ml, of donor CSF spiked with different HER2 expressing cell lines were tested for stability in MSB’s CellRescue Blood Collection Tube. For all volumes tested in the CellRescue Tube, average of 85% recovery of the SKBR3 cells and 100% presence of HER2 on the enriched cells was observed throughout the 5 day assessment period. Testing of the CTC/HER2 low assay in the various expressing HER2 cell lines demonstrated analytical sensitivity >70% and analytical specificity of 100%. Linearity testing showed reproducibility across the clinical range with an R2= 0.99. Testing of the assay using 3.0mls CSF, collected in the CellRescue Tube from 20 patients with mBC related LMC reliably demonstrated the presence of CTCs with HER2 expression. These data suggest that using the CELLSEARCH® CTC/HER2 assay in 3.0mls CSF, collected in MSB’s CellRescue Tube, provides the stability and sensitivity needed in a liquid biopsy test when taken from a lumbar puncture to guide improved management of patients with mBC related LMC.