TY - JOUR
T1 - Significance of circulating tumor cells in metastatic triple-negative breast cancer patients within a randomized, phase II trial
T2 - TBCRC 019
AU - Translational Breast Cancer Research Consortium (TBCRC)
AU - Paoletti, Costanza
AU - Li, Yufeng
AU - Muñiz, Maria C.
AU - Kidwell, Kelley M.
AU - Aung, Kimberly
AU - Thomas, Dafydd G.
AU - Brown, Martha E.
AU - Abramson, Vandana G.
AU - Irvin, William J.
AU - Lin, Nancy U.
AU - Liu, Minetta C.
AU - Nanda, Rita
AU - Nangia, Julie R.
AU - Storniolo, Anna M.
AU - Traina, Tiffany A.
AU - Vaklavas, Christos
AU - Van Poznak, Catherine H.
AU - Wolff, Antonio C.
AU - Forero-Torres, Andres
AU - Hayes, Daniel F.
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research. © 2015 American Association for Cancer Research.
PY - 2015/6/15
Y1 - 2015/6/15
N2 - 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 triplenegative (TN) MBC, and whether CTC apoptosis and clustering enhances the prognostic role of CTC. Experimental Design: CTC enumeration and apoptosis were 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-paclitaxel) with or without tigatuzumab. 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 of 52 (26.9%), and 13 of 49 (26.5%) patients who were evaluable had elevated CTC (≥5 CTC/7.5 mL whole blood) at baseline and at days 15 and 29, respectively. Patients with elevated versus 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 versus 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 versus 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 TNMBC patients. Elevated CTC at baseline and days 15 and 29 were prognostic, and reductions in CTC levels reflected response.
AB - 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 triplenegative (TN) MBC, and whether CTC apoptosis and clustering enhances the prognostic role of CTC. Experimental Design: CTC enumeration and apoptosis were 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-paclitaxel) with or without tigatuzumab. 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 of 52 (26.9%), and 13 of 49 (26.5%) patients who were evaluable had elevated CTC (≥5 CTC/7.5 mL whole blood) at baseline and at days 15 and 29, respectively. Patients with elevated versus 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 versus 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 versus 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 TNMBC patients. Elevated CTC at baseline and days 15 and 29 were prognostic, and reductions in CTC levels reflected response.
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U2 - 10.1158/1078-0432.CCR-14-2781
DO - 10.1158/1078-0432.CCR-14-2781
M3 - Article
C2 - 25779948
AN - SCOPUS:84940993817
SN - 1078-0432
VL - 21
SP - 2771
EP - 2779
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -