Determining circulating endothelial cells using CellSearch system during preoperative systemic chemotherapy in breast cancer patients

Eur J Cancer. 2011 Oct;47(15):2265-72. doi: 10.1016/j.ejca.2011.06.015. Epub 2011 Jul 5.

Abstract

Background: Circulating endothelial cells (CECs) have been studied as a biomarker for tumour progression and monitoring therapeutic effects. The CellSearch system is a semi-automated system that allows standardised analysis of CECs. This study assessed the clinical implications of CECs determined by the CellSearch system in breast cancer patients.

Methods: Seventy-six consecutive breast cancer patients (53 operable and 23 metastatic or recurrent) were enrolled for the study. Thirty-five patients with operable breast cancer received preoperative chemotherapy with a regimen based on anthracycline and/or taxane. CECs are defined as CD146(+)CD105(+)CD45(-)DAPI(+) cells in the system. CD34 expression was examined using the additional channel in the system.

Results: A majority (4539 of 5183 cells, 88%) of CECs from patients with operable breast cancer were CD34-positive. Triple-negative cancers showed higher baseline CEC and CD34(+)CEC counts than the other types (P=0.0387 and 0.0377, respectively). Low baseline CEC and CD34(+)CEC counts, and a low CD34 positive rate were associated with pathological complete response (pCR) of preoperative chemotherapy in patients with primary breast cancer (P=0.046, 0.027 and 0.01, respectively). In multivariate analyses, the CD34 positive rate was significant for pCR (P=0.021). During preoperative chemotherapy, CEC and CD34(+)CEC counts before each cycle of chemotherapy increased with taxane-based regimens (P=0.0018 and 0.0008, respectively) but not with anthracycline-based regimens.

Conclusions: Baseline CEC, in particular CD34(+)CEC, counts and the CD34 positive rate might be useful for the prediction of treatment response of preoperative chemotherapy in patients with operable breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Anthracyclines / administration & dosage
  • Antigens, CD / analysis
  • Antigens, CD34 / analysis*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Automation, Laboratory
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • CD146 Antigen / analysis
  • Chemotherapy, Adjuvant
  • Endoglin
  • Female
  • Humans
  • Immunomagnetic Separation*
  • Immunophenotyping / methods*
  • Japan
  • Leukocyte Common Antigens / analysis
  • Logistic Models
  • Microscopy, Fluorescence*
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplastic Cells, Circulating / drug effects*
  • Neoplastic Cells, Circulating / immunology
  • Neoplastic Cells, Circulating / pathology
  • Patient Selection
  • Predictive Value of Tests
  • Receptors, Cell Surface / analysis
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Young Adult

Substances

  • Anthracyclines
  • Antigens, CD
  • Antigens, CD34
  • Biomarkers, Tumor
  • CD146 Antigen
  • ENG protein, human
  • Endoglin
  • MCAM protein, human
  • Receptors, Cell Surface
  • Taxoids
  • Leukocyte Common Antigens
  • PTPRC protein, human