CTC enumeration and characterization: moving toward personalized medicine

Abstract

The primary cause of tumor-related death in breast cancer (BC) is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. The enumeration of circulating tumor cells (CTCs) represents an effective prognostic and predictive biomarker, which is able to monitor efficacy of adjuvant therapies, detect early development of (micro)metastases and at last, assess therapeutic responses of advanced disease earlier than traditional imaging methods. Moreover, since repeated tissue biopsies are invasive, costly and not always feasible, the assessment of tumor characteristics on CTCs, by a peripheral blood sample as a 'liquid biopsy', represents an attractive opportunity. The implementation of molecular and genomic characterization of CTCs could contribute to improve the treatment selection and thus, to move toward more personalized treatments. This review describes the current state of the art on CTC detection strategies, the evidence to demonstrate their clinical validity, and their potential impact for both future clinical trial design and, decision-making process in our daily practice.

Keywords: Breast cancer (BC); circulating tumor cells (CTCs); liquid biopsy; precision medicine.

Figures

Figure 1

Computer-generated reconstruction of CTC images by semi-automated fluorescence-based microscopy system (CellSpotter Analyzer). EpCAM-positive cells are treated with a nucleic acid dye 4’, 6-doamidino-2-phenylindole (DAPI), a leukocyte-specific anti-CD45 monoclonal antibody (CD45-APC) and epithelial-specific anti-cytokeratin 8, 18, and 19 antibodies (CK-PE). CTCs exhibit cytoplasmic expression of cytokeratin (second column), contain a nucleus that binds to the nucleic acid dye (third column) and they are CD45-negative (fourth column). The first column represents the composite of the cells. CTCs, circulating tumor cells; EpCAM, epithelial cell adhesion molecule.

Figure 2

Prognostic and predictive value of CTC level in neoadjuvant, adjuvant and metastatic setting. OS, overall survival; DMFS, distant metastasis free survival; DFS, disease free survival; BC, breast cancer; PFS, progression-free survival; CTCs, circulating tumor cells.