Detection of circulating tumor cells during follow-up of patients with early breast cancer: Clinical utility for monitoring of therapy efficacy

Scand J Clin Lab Invest. 2014 Mar;74(2):132-42. doi: 10.3109/00365513.2013.864784. Epub 2013 Dec 19.

Abstract

Introduction: Circulating tumor cells (CTCs) detection prior to and during therapy is considered as an independent and strong prognostic marker. The present study was designed to isolate and characterize CTCs in peripheral blood of an early breast cancer (BC) patient as a biomarker for monitoring treatments efficacy.

Materials and methods: In total, 54 early breast cancer patients undergoing neoadjuvant and/or adjuvant chemotherapy regimens were enrolled into a prospective study. CTC detection in blood was performed by AdnaTest BreastCancer(™) (AdnaGen AG, Germany), which is based on the detection of EpCAM, HER2 and MUC1 specific transcripts in enriched CTC-lysates. Additionally, cDNA from isolated CTCs and PBMC was used for qPCR gene expression analysis of TOP1, TOP2A, CTSD, ST6, CK19 and reference gene actin.

Results: We found that CTCs can be detected in the peripheral blood of approximately 31% of early stage breast cancer patients. The presence of CTCs was detected in 36% ER positive, 32% PR positive and 30% HER2 positive patients. We found no correlation between CTCs and tumor size, tumor grade, histological grade and receptor status. Only 7% of all patients remained CTCs positive after adjuvant therapy. Gene expression analysis revealed a particular heterogeneity of the studied genes.

Conclusions: In conclusion, CTC detection may be a promising early marker of disease progression potentially enhancing the difficult therapeutic decisions. Further studies should, however, clearly demonstrate its utility for both the prediction of outcome and monitoring the effect of treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Adhesion Molecules / genetics
  • Chemotherapy, Adjuvant
  • Drug Monitoring
  • Early Diagnosis
  • Epithelial Cell Adhesion Molecule
  • Female
  • Gene Expression
  • Genetic Heterogeneity
  • Humans
  • Middle Aged
  • Mucin-1 / genetics
  • Neoplasm Grading
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / genetics
  • Receptor, ErbB-2 / genetics
  • Tumor Burden

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • MUC1 protein, human
  • Mucin-1
  • Neoplasm Proteins
  • RNA, Messenger
  • ERBB2 protein, human
  • Receptor, ErbB-2