Abstract PD04-07: Monitoring Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC) during Neoadjuvant Combination of Trastuzumab and Bevacizumab with Chemotherapy in HER2 Overexpressing Inflammatory Breast Cancer (IBC): An Ancillary Study of BEVERLY 2 Multicenter Phase II Trial

Abstract

Abstract Introduction: CTC detection in peripheral blood is an independent prognostic factor in early breast cancer but with a low detection rate of 10% to 23% of the patients (B. Rack, ASCO 2010, FC Bidard, Ann Oncol 2010). Changes in the HER2 status of CTC compared to the primary tumor have been reported (Riethdorf S CCR 2010). Predictive value of CEC for response to anti-angiogenic agents is debated. 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 multicenter 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. Bevacizumab was stopped 4 weeks before and reintroduced 4 weeks (w) after mastectomy. All patients had non metastatic IBC and over expressed 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, before cycle 5, before and after surgery. Results: From Oct 2008 to Oct 2009, 52 patients were included in this study and 51 were evaluable for CTC. At baseline, 18 patients out of 51 had ≥ one detectable CTC (35.3%, 95%CI 22-48%, range 1 to 92). Pathological complete response rate according to local review was 33/47 (70%) or 15/22 (68%) for centrally reviewed cases. At baseline, CTC level was not correlated with CEC level, neither with other patients and tumor characteristics’ (age, nodal status, PeV) nor pCR (centrally reviewed in 24). All positive cases for CTC detection had HER2 positive CTC. Five pts out of 18 (28%) had both HER2+ and HER2 negative CTCs in their blood. A lower level of CEC (< 20/4ml) before C5 could be associated with a higher probability of pCR (Khi2 test, p=0.053). Conclusion: We observed a high CTC detection rate of 35% in this population of patients with HER2+ IBC and a dramatic drop in CTC level during treatment in concordance with the high efficiency of this combination of chemotherapy and targeted therapy. We observed heterogeneity in the HER2 status of CTC in some patients. CEC levels increased progressively during neoadjuvant treatment and decreased after its interruption. Longer follow-up will show if CTC and CEC variations are early predictive factors for this highly efficient combination in HER2+ IBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-07.