Significance of Circulating Tumor Cells in metastatic triple negative breast cancer patients within a randomized, phase II trial: TBCRC 019

Purpose: Circulating Tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). We tested whether EpCAM based capture system (CellSearch®) is effective in patients with triple negative (TN) MBC, and whether CTC-apoptosis and clustering enhances the prognostic role of CTC. Experimental Design: CTC enumeration and apoptosis was determined using the CXC CellSearch® kit at baseline and days 15 and 29 in blood drawn from TN MBC patients who participated in a prospective randomized phase II trial of nanoparticle albumin-bound paclitaxel (nab-PAC) with or without tigatuzumab (TIG). Association between levels of CTC and patient outcomes was assessed using logistic regression, Kaplan Meier curves, and Cox proportional hazards modeling. Results: Nineteen of 52 (36.5%), 14/52 (26.9%), and 13/49 (26.5%) patients who were evaluable had elevated CTC (≥5CTC/7.5 ml WB) at baseline, days 15 and 29, respectively. Patients with elevated vs. not elevated CTC at each time point had worse progression free survival (PFS) (p=0.005, 0.0003, 0.0002, respectively). The odds of clinical benefit response for those who had elevated vs. low CTC at baseline and days 15 and 29 were 0.25 (95% CI: 0.08-0.84, p=0.024), 0.19 (95% CI: 0.05-0.17, p=0.014), and 0.06 (95% CI: 0.01-0.33, p=0.001), respectively. There was no apparent prognostic effect comparing CTC-apoptosis vs. non-apoptosis. Presence of CTC-cluster at day 15, and day 29 was associated with shorter PFS. Conclusions: CTC were detected using CellSearch® assay in approximately one-third of TN MBC patients. Elevated CTC at baseline and days 15 and 29 were prognostic, and reductions in CTC levels reflected response.