Mesenchymal Characterization: Alternative to Simple CTC Detection in Two Clinical Trials

Background: Breast cancer is one of the most common malignancies in women. Approximately 25% of patients with early-stage disease will develop metastatic recurrence. Two clinical trials were undertaken in order to detect circulating tumor cells (CTCs) in primary breast cancer. Patients and Methods: Four-hundred patients with early breast cancer were enrolled in the trial. After enrichment from their peripheral blood, their CTCs were characterized by gene expression of cancer cell markers. Results: CTCs had a predominant epithelial phenotype in 8.75% of patients and de- differentiated characteristics (mesenchymal, stem phenotypes alone or both) in 37.6%. Conclusion: Tumor epithelial cells undergoing epithelial-mesenchymal transition give rise to cells with mesenchymal aggressive phenotype. Detection of mesenchymal and cancer stem cells, which are tumor- initiating cells, is more relevant than simple counting of CTCs to assess their presence in the blood of patients with breast cancer. This study will be the basis for future evaluation of the outcome of the disease and the prognostic value of early- detected CTCs. Detection of circulating tumor cells (CTCs) has been recently developed and can be considered as a prognostic tool (1). A limited number of markers are currently used for the isolation