Multiple Biomarker Expression in Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer (MBC) Patients (Pts).

Abstract

Abstract Background: Numeration of CTCs from MBC pts is predictive of outcome. Quantitative changes in CTC-s are currently tested for their potential to monitor therapy (Rx). Biomarker characterization of CTCs may be a useful adjunctive guide for Rx selection. Method: At the COHCC between 5/1/2008 and 4/31/09, consecutively treated pts with newly diagnosed/or progressing MBC were accrued. Blood samples (10-40 ml) were procured prior to or during systemic Rx, and were sent to PARC for analysis. A novel high-speed scanning instrument located CTCs from cytokeratin (CK) labeling enabling high resolution images to be selectively acquired using digital microscopy. From these images, CTCs were identified by CK, DAPI (nuclear marker) and CD45, and protein expression levels were determined for HER2, ER, ERCC1 and EGFR. Cell lines with expression of each marker were used for normalization of the cell intensities, and a scoring system was used to account for relative number and expression levels of markers on the CTCs. Results: Of 21pts tested 81% were found to have detectable CTCs. CTCs were further analyzed from 13 such pts, some of whom had multiple specimens. Expression of EGFR and ERCC1 were detected in 77% and 92% of specimens tested. Expression of HER2 was detected in 47% and ER in 91% in samples tested. Discordance rates for the expression of the above 4 markers on the primary tumors vs. CTC were measured either before, during systemic treatment, or at progression on therapy. We observed significant discordance rates for all markers tested:ER 36%; ERCC1:20%; EGFR:60%; and HER2: 50%, respectively. Conclusions: Multiplex tumor marker testing of CTCs from pts with MBC is feasible. Following additional validation of expression patterns and the high discordance rates observed between CTCs and primary or metastatic tumor sites, prospective trials incorporating CTC expression into personalized treatment strategies may be justified. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3007.