The biological information obtainable from circulating tumor cells.

The reliable detection of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) is possible by using immunomagnetic separation and subsequent characterization with the CellSpotter analyzer (Veridex LLC, a Johnson & Johnson company, Warren, NJ, USA). This technology is becoming a standard tool for the 'real-time' assessment of prognosis and response to treatment. The prognostic value is independent of the line of therapy (e.g. first-line versus second-line or more), site of metastasis (e.g. visceral versus soft tissue/bone), and subtype of disease (e.g. basal vs. luminal). Moreover, CTCs detection has been recently associated with worse outcome also in patients with primary breast cancer that have completed neoadjuvant or adjuvant therapy. These findings suggest the need to further investigate the biology of CTCs. Several investigators have recently focused on determining the feasibility of performing the genotypic characterization of CTCs and correlate it with the expression of similar genes in primary or metastatic lesions. Some of the studies have used a recently introduced detection technology combining EpCAM-enrichment and PCR analysis (AdnaTest Breast Cancer, Adnagen AG, Germany). The studies seem to indicate that CTCs differ in the expression of hormone receptors and HER-2 compared to primary disease. Furthermore, some of the phenotypic assessment seems to suggest that a fraction of CTCs could be identified as cancer stem cells. Those data suggest interesting observations in the biology of those cells and indicate the possibility to evaluate targeted therapies based on the genomic profiling of CTCs, particularly with regards to HER-2 determination.