98IN - Circulating Tumour Cells: Isolation, Enrichment and Clinical Value in Breast Cancer

Abstract

ABSTRACT Circulating Tumor Cells (CTCs) detection is challenging because these are rare tumor cells in a background of millions of blood cells. Therefore, an enrichment step is often applied based on their biological (expression of Epithelial Cell Adhesion Molecule, EpCAM) or physical properties (size, deformability, density and electric charges). CellSearch (Janssen Diagnostics, Raritan, NJ, USA) is the only technology that has been cleared by Food and Drug Administration (FDA) for CTC enumeration as an aid in monitoring patients with metastatic breast, colorectal and prostate cancer. The detection of at least 5 CTCs/7.5 ml of blood using CellSearch in progressing patients with metastatic breast cancer (MBC) was associated with increased risk of death in a US study of 177 patients published in 2004. These results were recently confirmed in a European metaanalysis of almost 2000 patients individual data providing level I evidence that CTC detection is associated with worse outcome in MBC. The most well known trial to test the clinical utility of CTCs in MBC is the SWOG 0500 that was recently published. The investigators asked whether an early change of an ineffective 1st line chemotherapy based on CTCs can result in improvement in overall survival (primary endpoint). The trial confirmed the prognostic value of CTCs but did not meet its primary endpoint. Ongoing trials such as the STIC CTC, DETECT III and COMETI will provide an answer on the clinical utility of CTCs in MBC. More recently, 4 studies including almost 3000 patients have shown that CTC detection using CellSearch is associated with worse outcome in early breast cancer. The ongoing Treat CTC trial is testing CTC elimination as an early signal of trastuzumab activity in HER2-negative non-metastatic breast cancer. Beyond enumeration, CTC characterization may be used as a liquid biopsy to assess and understand treatment resistance. The analysis of plasma circulating tumor DNA (ctDNA) using technologies such as next generation sequencing or droplet digital polymerase chain reaction could be an attractive alternative for monitoring treatment effect. CTCs, despite being more laborious to isolate, represent intact tumor cells that can be analyzed at the DNA, RNA and protein level, thus providing complementary information to ctDNA. Disclosure: M. Ignatiadis: I have received consultancy fees from Janssen Diagnostics, I will discuss investigational use of trastuzumab in my presentation.