Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study

J Transl Med. 2018 Oct 20;16(1):287. doi: 10.1186/s12967-018-1663-8.

Abstract

Background: Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy.

Methods: Twenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs.

Results: Numbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively).

Conclusions: Our data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM).

Keywords: Breast cancer; Circulating tumour cell; Epithelial mesenchymal transition; Eribulin; Liquid biopsy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Cell Size
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition* / drug effects
  • Female
  • Furans / pharmacology
  • Furans / therapeutic use*
  • Humans
  • Kaplan-Meier Estimate
  • Ketones / pharmacology
  • Ketones / therapeutic use*
  • Logistic Models
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / pathology*
  • Pilot Projects
  • Treatment Outcome

Substances

  • Furans
  • Ketones
  • eribulin