Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy

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Abstract

Antiangiogenic agents and therapeutic strategies have entered the clinical oncology arena. The classical tumor size measurements defined to monitor efficacy of chemotherapy, however, might not be appropriate for these newer therapeutics. We previously found that circulating endothelial cells (CECs) were increased in number and more viable in cancer patients compared with control subjects. We investigated the correlation between CEC kinetics and clinical outcome in patients with advanced breast cancer receiving metronomic chemotherapy, a therapeutic strategy associated with antiangiogenic activity and anticancer efficacy. CEC number and viability were measured by flow cytometry in patients and in preclinical models. CECs were decreased in patients for whom no overall clinical benefit (defined as a clinical response or a stable disease) was observed compared with those who had a clinical benefit (P = .015). This difference was due to an increased fraction of apoptotic CECs in patients with a clinical benefit. Univariate and multivariate analyses indicated that CEC values greater than 11/μL were associated with a longer progression-free survival (P = .001) and an improved overall survival (P = .005). Preclinical models indicated that the source of apoptotic CECs was most likely the tumor vasculature. CEC kinetics and viability are very promising as predictors of clinical response in patients undergoing metronomic chemotherapy.

Original languageEnglish
Pages (from-to)452-459
Number of pages8
JournalBlood
Volume108
Issue number2
DOIs
Publication statusPublished - Jul 15 2006

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Chemotherapy
Endothelial cells
Cell Survival
Endothelial Cells
Breast Neoplasms
Drug Therapy
Kinetics
Survival
Tumors
Neoplasms
Angiogenesis Inhibitors
Oncology
Medical Oncology
Flow cytometry
Disease-Free Survival
Flow Cytometry
Therapeutics
Multivariate Analysis
Cell Count

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy",
abstract = "Antiangiogenic agents and therapeutic strategies have entered the clinical oncology arena. The classical tumor size measurements defined to monitor efficacy of chemotherapy, however, might not be appropriate for these newer therapeutics. We previously found that circulating endothelial cells (CECs) were increased in number and more viable in cancer patients compared with control subjects. We investigated the correlation between CEC kinetics and clinical outcome in patients with advanced breast cancer receiving metronomic chemotherapy, a therapeutic strategy associated with antiangiogenic activity and anticancer efficacy. CEC number and viability were measured by flow cytometry in patients and in preclinical models. CECs were decreased in patients for whom no overall clinical benefit (defined as a clinical response or a stable disease) was observed compared with those who had a clinical benefit (P = .015). This difference was due to an increased fraction of apoptotic CECs in patients with a clinical benefit. Univariate and multivariate analyses indicated that CEC values greater than 11/μL were associated with a longer progression-free survival (P = .001) and an improved overall survival (P = .005). Preclinical models indicated that the source of apoptotic CECs was most likely the tumor vasculature. CEC kinetics and viability are very promising as predictors of clinical response in patients undergoing metronomic chemotherapy.",
author = "Patrizia Mancuso and Marco Colleoni and Angelica Calleri and Laura Orlando and Patrick Maisonneuve and Giancarlo Pruneri and Alice Agliano and Aron Goldhirsch and Yuval Shaked and Kerbel, {Robert S.} and Francesco Bertolini",
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T1 - Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy

AU - Mancuso, Patrizia

AU - Colleoni, Marco

AU - Calleri, Angelica

AU - Orlando, Laura

AU - Maisonneuve, Patrick

AU - Pruneri, Giancarlo

AU - Agliano, Alice

AU - Goldhirsch, Aron

AU - Shaked, Yuval

AU - Kerbel, Robert S.

AU - Bertolini, Francesco

PY - 2006/7/15

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N2 - Antiangiogenic agents and therapeutic strategies have entered the clinical oncology arena. The classical tumor size measurements defined to monitor efficacy of chemotherapy, however, might not be appropriate for these newer therapeutics. We previously found that circulating endothelial cells (CECs) were increased in number and more viable in cancer patients compared with control subjects. We investigated the correlation between CEC kinetics and clinical outcome in patients with advanced breast cancer receiving metronomic chemotherapy, a therapeutic strategy associated with antiangiogenic activity and anticancer efficacy. CEC number and viability were measured by flow cytometry in patients and in preclinical models. CECs were decreased in patients for whom no overall clinical benefit (defined as a clinical response or a stable disease) was observed compared with those who had a clinical benefit (P = .015). This difference was due to an increased fraction of apoptotic CECs in patients with a clinical benefit. Univariate and multivariate analyses indicated that CEC values greater than 11/μL were associated with a longer progression-free survival (P = .001) and an improved overall survival (P = .005). Preclinical models indicated that the source of apoptotic CECs was most likely the tumor vasculature. CEC kinetics and viability are very promising as predictors of clinical response in patients undergoing metronomic chemotherapy.

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