Abstract 2233: Detection of HER2 positive Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC) in an ancillary study of BEVERLY 2 multicentric phase II trial of neoadjuvant chemotherapy combined with trastuzumab and bevacizumab in HER2 overexpressing inflammatory breast cancer (IBC)
Authors: Pierga Jean-Yves , Mathiot Claire , Bidard François-Clément , Petit Thierry , Delozier Thierry , Ferrero Jean-Marc , Campone Mario , Gligorov Joseph , Lerebours Florence , Roché Henri , Bobadilla Luz , Viens Patrice 
Published: February 2011

Abstract
Introduction: CTCs in peripheral blood are an independent prognostic factor in primary breast cancer but with a low detection rate of 10% to 23% of the patients (B. Rack, ASCO 2008, FC Bidard, Ann Oncol 2009) in the absence of distant metastasis. Changes in the HER2 status of CTC compared to the primary tumor have been reported (M. Pestrin BCRT 2009). Predictive value of CEC for response to anti-angiogenic agents is debated. CTC and CEC were monitored in this trial evaluating the combination of bevacizumab (directed against VEGF) with chemotherapy and trastuzumab in the neoadjuvant setting of HER2 positive IBC.
Material and methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively in IBC (T4d) patients enrolled in the phase II multicentric trial, BEVERLY 2. This study is evaluating the efficacy of bevacizumab (15mg/kg q3w given concurrently) in combination with sequential neoadjuvant chemotherapy of 4 cycles of FEC followed by 4 cycles of Docetaxel-Trastuzumab. All patients had early breast cancer and overexpressed HER2 (3+ in IHC or FISH +). The CellSearch™ System, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) and anti-HER2 fluorescently staining for CTC and CD146 IMS and CD105 staining for CEC, was used at baseline and during treatment.
Results: From Oct 2008 to Oct 2009, 52 patients were included in this study. At baseline, 18 patients out of 52 had ≥ one detectable CTC (35%, 95%CI 22-48%), 10 (19%) ≥ 2 CTC and 7 (13%) ≥ 5CTC per 7.5ml. Median CTC count was 2 (range 1-92) and median CEC was 8 (1-727). No correlation was found between CTC and CEC levels at baseline. All positive cases for CTC detection had HER2 positive CTC. A total of 246 CTCs has been detected and 215 were HER2+ cells (87%). Five pts out of 18 (28%) had both HER2+ and HER2 negative CTCs in their blood. At the time of analysis, data are available for 41 pts after 4 cycles of neoadjuvant chemotherapy combined with bevacizumab. We observed a dramatic drop in CTC level with only 3 pts with one detected CTC (6%). CEC level decreased in 10 and increased in 27 patients (NA in 4) with a median of CEC of 24 (range 1-185) before cycle 5 and introduction of trastuzumab.
Conclusion: It is possible to monitor CTC, HER2 status of CTC and CEC with the same available immuno-magnetic technology in a multicentric trial. We observed a high CTC detection rate of 35% in this population of patients with HER2+ IBC and a dramatic drop in CTC level after 4 cycles of chemotherapy combined with bevacizumab suggesting specific impact of this antibody on CTC detection. We observed heterogeneity in the HER2 status of CTC in some patients. Presence of HER2 negative CTC population will be explored as an indicator of resistance to trastuzumab when follow-up data are available.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2233.