Clinical Relevance and Biology of Circulating Tumor Cells

Natalia Bednarz-Knoll; Catherine Alix-Panabières; Klaus Pantel


Breast Cancer Res. 2011;13(6):228 

In This Article

Abstract and Introduction


Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer.


Detection of circulating tumor cells (CTCs) in peripheral blood and disseminated tumor cells (DTCs) in bone marrow of tumor patients has become an active area of translational cancer research, with numerous groups developing new diagnostic assays and more than 200 clinical trials incorporating CTC counts as a biomarker in patients with various types of solid tumors. Among these activities, breast cancer has played the most prominent role as a 'driver' of research on CTCs/DTCs. The clinical relevance of DTCs is already well-established[1,2] and has been confirmed by different large-scale studies, including a pooled analysis on almost 5,000 patients.[3] Aspirations of bone marrow, a common homing organ for many types of solid tumors,[1,4] are part of the routine screening of leukemia patients and are much less difficult to perform than biopsies of other organs (for example, lungs or liver). Nevertheless, it is still a painful and invasive procedure that is not comfortable for patients and, due to this fact, has not yet been accepted for routine diagnosis of solid tumors. In contrast, CTCs are easier to obtain by peripheral blood sampling, which can be repeated frequently, allowing real-time monitoring of metastatic progression. Thus, it seems that peripheral blood might serve as a perfect alternative source of material to diagnose cancer patients, and CTC analysis in cancer patients has thus been termed a 'liquid biopsy'.[5]

On the other hand, detection of CTCs is hampered by the still uncertain biology of these cells, which most likely inherit a heterogeneous malignant potential to home and give rise to overt metastasis in secondary organs. Even modern technologies that have been applied to isolate and characterize CTCs still need to be improved.[6] Although recent results on significant associations between the presence of CTCs and subsequent occurrence or progression of metastases are encouraging, the clinical relevance and utility of CTCs merit further investigation and confirmation by multicenter trials.

Developments in CTC/DTC technologies over the past few years have been impressive. This review will recapitulate the current knowledge on CTCs in breast cancer patients with a focus on the biology and clinical relevance of these cells.


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