Significance of circulating tumor cells in metastatic triple-negative breast cancer patients within a randomized, phase II trial: TBCRC 019

Translational Breast Cancer Research Consortium (TBCRC)

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2771-2779
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number12
DOIs
StatePublished - Jun 15 2015
Externally publishedYes

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Triple Negative Breast Neoplasms
Circulating Neoplastic Cells
Apoptosis
Breast Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Significance of circulating tumor cells in metastatic triple-negative breast cancer patients within a randomized, phase II trial : TBCRC 019. / Translational Breast Cancer Research Consortium (TBCRC).

In: Clinical Cancer Research, Vol. 21, No. 12, 15.06.2015, p. 2771-2779.

Research output: Contribution to journalArticle

@article{b0227d600f7545259f35d7eac8f6df43,
title = "Significance of circulating tumor cells in metastatic triple-negative breast cancer patients within a randomized, phase II trial: TBCRC 019",
abstract = "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.",
author = "{Translational Breast Cancer Research Consortium (TBCRC)} and Costanza Paoletti and Yufeng Li and Mu{\~n}iz, {Maria C.} and Kidwell, {Kelley M.} and Kimberly Aung and Thomas, {Dafydd G.} and Brown, {Martha E.} and Abramson, {Vandana G.} and Irvin, {William J.} and Lin, {Nancy U.} and Liu, {Minetta C} and Rita Nanda and Nangia, {Julie R.} and Storniolo, {Anna M.} and Traina, {Tiffany A.} and Christos Vaklavas and {Van Poznak}, {Catherine H.} and Wolff, {Antonio C.} and Andres Forero-Torres and Hayes, {Daniel F.}",
year = "2015",
month = "6",
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doi = "10.1158/1078-0432.CCR-14-2781",
language = "English (US)",
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pages = "2771--2779",
journal = "Clinical Cancer Research",
issn = "1078-0432",
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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.

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

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JO - Clinical Cancer Research

JF - Clinical Cancer Research

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