Circulating Tumor Cells
TERMINOLOGY
Abbreviations
Circulating tumor cell (CTC)
Definitions
Pathologic staging of breast cancer is clinically useful in determining course of disease
Identification of tumor cells in lymph nodes and bone marrow indicates increased risk for recurrence/metastasis
Indication for systemic treatment as part of therapeutic regimen
Significant number of early stage breast cancers will recur following theoretically curative surgical excision
Suggests that current clinical staging is inadequate for some patients
More sensitive methods for determining tumor cell dissemination and risk for metastasis needed
Tumor cells spread to distant sites through venous and lymphatic circulation before development of clinically detectable disease
Number of investigators have attempted to look for circulating tumor cells in peripheral blood as surrogate for early dissemination
Detection of CTCs may reflect aggressiveness of breast tumor
May assist in therapeutic decisions in patients with breast cancer
CTCs may have role as surrogate markers to monitor treatment response
Recent technical advances have made reliable detection of CTCs possible
Target Gene or Antigen
CTCs are rare findings within blood stream requiring specific and sensitive methodologies for detection
Strategies for detection have attempted to exploit differences between epithelial cells and blood or between benign and malignant cells
Most technical methods for detecting CTCs rely on combination of cell enrichment and detection step
Immunomagnetic bead coated with antibodies can be used to tag and separate epithelial cells from whole blood
These isolated cells are then characterized as CTC based on detection of some biologic marker
In breast cancer, RT-PCR for cytokeratin, MUC1, CEA, mammaglobin, and HER2 have been used to identify punitive CTC
IHC and immunofluorescence for epithelial markers have also been used to identify CTCs
Types of Tests
Blood represents convenient clinical sample, is easily obtained, and has been the most extensively studied for CTCs
Some studies have suggested that assessment of bone marrow for tumor cells may yield better predictor of disease outcome
Current methods are limited to the ability to identify and count CTCs
Newer methods under development are seeking to capture viable tumor cells from the circulation
Isolated viable CTCs may be able to be grown in tissue culture
Viable CTCs can undergo further molecular analysis
May provide clinically useful information
CLINICAL ISSUES
CTC Technology
Detection of circulating tumor cells may represent early indication of micrometastasis
May be useful in identification of aggressive tumors, which are able to shed cells into bloodstream
Current data are unclear on how this information can be used in breast cancer management
Commercially available CTC detection methodology (Cell Search assay [Veridex; Raritan, NJ])
Assay utilizes immunomagnetic selection to enrich for CTC
Immunomagnetic selection followed by immunofluorescent detection of CTCs
Epithelial markers such as cytokeratin and HER2 used to identify tumor cells
Nuclear staining with 4′-6-diamidino-2-phenylindole used to help identify intact cells
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