Abstract PD04-06: Changes in Circulating Tumor and Endothelial Cells in Peripheral Blood of Patients Treated in the Neoadjuvant Chemotherapy Plus Targeted Treatment Breast Cancer Study “GeparQuinto”
Authors: Riethdorf S , Mueller V , Mauermann O , Rau T , Loibl S , Eidtmann H , Solbach C , Tesch H , Schrader I , Kittel K , Fehm T , Holms F , Untch M , von Minckwitz G , Pantel K. 
Published: April 2011

Abstract
Background: The GeparQuinto study is a phase III neoadjuvant therapy (NT) study exploring the integration of Trastuzumab and Lapatinib for HER2-positive patients and Bevacizumab and Everolimus (RAD001) for HER2-negative patients. Predictive factors for these new treatment options are required. Therefore, we investigated in a subanalysis the potential of circulating tumor cells (CTC) and circulating endothelial cells (CEC) in peripheral blood during the course of NT.
Material and Methods: Whole blood was taken prior to start of NT, after 4 cycles of NT and after NT prior to surgery. CTC and CEC were prospectively measured with the CellSearch® system using 15 mL and 4 mL blood, respectively that was also applied for HER2 status determination of CTC. Study recruitment will finish approximately in July 2010. Results: From 419 patients currently included in this subanalysis (23% with HER2-positive primary tumor), 364 patients had a sample prior to NT, 268 patients after 4 cycles NT and 213 patients after completion of NT. Before therapy, ≥1 CTC/15mL were detected in 82/364 patients (22.5%, range 1-112; mean 8.01; median 2), after 4 cycles of NT in 37/268 patients (13.8%, range 1-170; mean 6.4; median 1) and before surgery in 22/210 patients (10.5%; range 1-7; mean 1.73; median 1). Five or more CTC/15mL were found at these three time points in 8%, 2.2% and 0.5%, respectively. Significant decreases in CTC incidence and CTC numbers per patient were observed during therapy from baseline to the 2nd analysis after 4 cycles of NT (p=0.0081), and these decreases further continued to the 3rd analysis after completing NT (P&lt;0.0001). In about 20% of all analyzed CTC-positive cases, a discrepancy between the HER2 status of CTC and the primary tumors (either only HER2-negative CTC in patients with HER2-positive primary tumors or at least 1 CTC with strong HER2 expression in patients with HER2-negative primary tumors) was detected. Interestingly, changes in CEC counts under NT were inverse to changes in CTC. CEC numbers ranged between 0 and 7000/4mL (median 12) at baseline, between 1 and 1648 (median 29) after 4 cycles of NT, and between 6 and 5000 (median 163.5) before surgery after completion of NT. A marked increase of CEC numbers during the course of treatment (P&lt;0.0001) was observed. However, numbers of CEC at baseline and after completion of NT were independent of each other (p=0.81). Changes in CTC and CEC are currently being correlated to tumor and patient characteristics. Conclusions: This is the largest study investigating in parallel both CTC and CEC counts in the context of NT combined with targeted therapy. Our study confirms discrepancies between the HER2 status in CTC and the corresponding primary tumors. Furthermore, our results indicate that NT causes significant but opposite changes in CTC and CEC counts.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-06.