Clinical role of detecting circulating tumor cells

Using ultrasensitive molecular or immunological/cytometric approaches, identification of circulating tumor cells (CTC) thus far undetectable at primary diagnosis even by high resolution imaging technologies is feasible. Results from several clinical studies revealed that in breast cancer patients with metastatic disease positivity for CTC is associated with worse prognosis. Thus, information obtained from CTC research might support clinicians in assessing individual prognosis, stratifying patients at risk to systemic adjuvant anti-cancer therapies, early response evaluation and monitoring therapeutic efficacy. At present, the CellSearchTM system combining automated capturing of CTC, immunostaining and image analysis is the only standardized technology approved by the FDA for the detection of CTC in patients with metastatic breast, colorectal and prostate cancer [1–3]. However, evidence has emerged that most currently used CTC detection methods still lack sensitivity or specificity to find all CTC especially those that have lost epithelial features, e.g. in the course of epithelial-mesenchymal transition [4–7]. Therefore special emphasis is placed to the development of innovative new strategies with the capacity to track additional CTC and to identify those with the potential to initiate metastasis. In this context, discovery of approaches enabling further phenotypical and molecular characterisation of CTC, e.g., analysis of single cell whole genomes, next generation sequencing and gene expression analysis on CTC is pivotal particularly in view of the development of new personalized targeting therapies. It is also worth mentioning that detection and characterization of CTC within translational research projects has entered clinical trials also enrolling patients with early breast cancer. First promising results on CTC detection especially within treatment regimens including targeted therapy, e.g., trastuzumab directed against HER2 in breast cancer patients receiving neoadjuvant or adjuvant therapy have been published recently [8–11]. Furthermore, characterization of the HER2 status of CTC might help identifying additional patients profiting from an anti-HER2 treatment and getting insights into therapy-induced selection of CTC.