Enumeration and molecular characterization of circulating tumor cells as an innovative tool for companion diagnostics in breast cancer

ABSTRACT

Introduction

Circulating tumor cells (CTC) and more recently, CTC clusters are implicated as a fundamental mechanism by which tumor cells break away from the primary site and travel to distant sites. Enumeration of CTC and CTC clusters represents a new approach to prognosis, prediction, and response to therapy in patients with early and metastatic breast cancer. Several recent studies have shown the predictive importance of monitoring CTCs levels in progression-free and overall survival in breast cancer patients. This review will focus on CTC enumeration and characterization in breast cancers.

Areas covered

We will provide a historical perspective and clinical background of CTC detection in peripheral blood. The current methodologies for studying CTCs and newer technologies for CTC detection will be reviewed together with the current state of the art of CTCs as a biomarker in risk stratification and prognostication in breast cancers.

Expert opinion

Currently, there is an FDA approved CTC assessment method for clinical use. While CTC enumeration, is a marker for prognostication and survival, molecular characterization of CTC, may be more accurate in monitoring response to treatment due to tumor heterogeneity rather than the tumor phenotype at the primary or metastatic sites.

KEYWORDS:

• Circulating Tumor Cells (CTC)
• breast cancer
• enumeration
• characterization
• ctc Cluster
• ctc Heterogeneity

Article highlights

• Enumeration and characterization of CTC and CTC clusters represent a promising approach to prognosis, prediction, and response to therapy in patients with early and metastatic breast cancer.

• Changes in CTC counts during the course of therapy have been shown to predict response to treatment in numerous studies in breast cancers; however, the clinical application of CTC has not been widely accepted due to potential limitations related to CTC capture techniques to detect CTC in the transition from epithelial to mesenchymal phenotype.

• This review summarizes the various methodologies for CTC detection and overview of current ongoing clinical trials using CTC for clinical treatment decisions in breast cancers.

Declaration of interest

Malini Harigopal is a member of the Veridex pathology virtual advisory board to discuss clinical input among experts in the CTC field in US and Europe to set guidelines for biomarkers that should be considered when designing assays and improving the current platform for next generation of circulating tumor cell (CTC) technology platform 2012. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper is not funded.