Abstract P2-02-06: Impact of apoptotic circulating tumor cells in metastatic breast cancer

Abstract

Abstract Background Circulating tumor cells (CTC) are a heterogeneous cell population and an independent negative prognostic factor for progression-free (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC). The study aimed to prospectively assess CTC status for the subtypes apoptotic CTC (aCTC) and intact CTC (iCTC) at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C). Changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) were evaluated for their utility in predicting response, progression-free (PFS) and overall survival (OS). Methods 423 MBC patients were included in a prospective trial prior to a new regimen of treatment. Intact and apoptotic CTC were analyzed at baseline (CTCBL) and after one cycle of systemic therapy (CTC1C) using CellSearch™ (Veridex) and morphologic criteria. Samples with ≥5 CTC/7.5ml blood were regarded as positive. Therapy response was assessed using the RECIST-criteria on three-monthly radiological controls. CTCKIN were characterized by ≥25% change from CTCBL to CTC1C to differentiate stable, increased and decreased CTC kinetic. Results 35% of patients were iCTCBL-positive and 28% aCTCBL-positive at baseline (CTCBL). PFS and OS differ significantly between the iCTCBL-positive and the iCTCBL-negative group (PFS 4.5 vs. 8.0; OS 12.5 vs. 27.2 (months)). Positive aCTC in conjunction with positive iCTCBL at baseline has worst prognostic impact (PFS 6.3; OS 8.7). Regarding the CTCKIN (BL to 1C), aCTC-decrease (≥25%) is a positive prognostic factor compared to aCTC-stable and aCTC-increase (PFS 7.6 vs. 3.7; 3.3 and OS 21.0 vs. 4.8; 5.7). Decreasing aCTCKIN shows favorable prognostic impact versus decreasing iCTCKIN (PFS 7.6 vs. 5.9 and OS 21.0 vs 16.4). Conclusion Elevated aCTC levels at baseline have an unfavorable prognostic impact on both OS and PFS in conjunction with elevated iCTC. Additionally, the decrease of aCTC is a relevant prognostic value for systemic therapy response. aCTCKIN allows better differentiation for therapy response in patients with positive CTC-status at baseline. Differentiated enumeration of intact and apoptotic CTC should be considered in clinical application. Citation Format: Wallwiener M, Deutsch TM, Riethdorf S, Hartkopf AD, Taran F-A, Trumpp A, Brucker S, Schütz F, Rom J, Pantel K, Schneeweiss A. Impact of apoptotic circulating tumor cells in metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-02-06.