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Circulating tumor cells in breast cancer: a tool whose time has come of age.

Swaby RF, Cristofanilli M - BMC Med (2011)

Bottom Line: Circulating tumor cells (CTCs) are isolated tumor cells disseminated from the site of disease in metastatic and/or primary cancers, including breast cancer, that can be identified and measured in the peripheral blood of patients.As recent technical advances have rendered it easier to reproducibly and repeatedly sample this population of cells with a high degree of accuracy, these cells represent an attractive surrogate marker of the site of disease.In this mini-review, we review CTCs in metastatic breast cancer, and discuss their clinical utility for assessing prognosis and monitoring response to therapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. ramona.swaby@fccc.edu

ABSTRACT
Circulating tumor cells (CTCs) are isolated tumor cells disseminated from the site of disease in metastatic and/or primary cancers, including breast cancer, that can be identified and measured in the peripheral blood of patients. As recent technical advances have rendered it easier to reproducibly and repeatedly sample this population of cells with a high degree of accuracy, these cells represent an attractive surrogate marker of the site of disease. Currently, CTCs are being integrated into clinical trial design as a surrogate for phenotypic and genotypic markers in correlation with development of molecularly targeted therapies. As CTCs play a crucial role in tumor dissemination, translational research is implicating CTCs in several biological processes, including epithelial to mesenchymal transition. In this mini-review, we review CTCs in metastatic breast cancer, and discuss their clinical utility for assessing prognosis and monitoring response to therapy. We will also introduce their utility in pharmacodynamic monitoring for rational selection of molecularly targeted therapies and briefly address how they can help elucidate the biology of cancer metastasis.

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Related in: MedlinePlus

(a) Schematic of Cell Tracks CTC separation system and (b) Detection of CTC. a. Epithelial cells are isolated from peripheral blood using antibodies to Ep-CAM conjugated to magnetic particles. Cells are then analyzed to determine the number of CTC. b. Detection of CTC. Two intact CTC are shown in the left panel, 33 damaged CTC in the central panel, and 6 cellular fragments in the right panel.
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Figure 1: (a) Schematic of Cell Tracks CTC separation system and (b) Detection of CTC. a. Epithelial cells are isolated from peripheral blood using antibodies to Ep-CAM conjugated to magnetic particles. Cells are then analyzed to determine the number of CTC. b. Detection of CTC. Two intact CTC are shown in the left panel, 33 damaged CTC in the central panel, and 6 cellular fragments in the right panel.

Mentions: CTCs are now generally defined as nucleated cells lacking CD45 and expressing cytokeratin [9,10]. Specifically, an antibody to the surface epithelial cell adhesion molecule (epCAM) identifies cells of epithelial origin circulating within the blood. Additionally, cytokeratin antibodies further distinguish CTCs as those that are not white blood cells (i.e. - CD45 negative) and select for carcinomas (i.e. - anti-CK8, anti-CK18, anti-CK19). Although multiple commercially available methods for isolating CTCs exist [11,12], the CellSearch™ system (Veridex Corporation, Warren, NJ) is the only FDA approved system for clinical use with reproducible results across many different laboratories. The CellSearch™ system has been fully described elsewhere [13]; but in summary, the system uses serum enriched for nucleated cells expressing epithelial-cell adhesion molecules, and fluorescently labels them for eventual detection by semi-automated fluorescence-based microscopy. (Figure 1) In this minireview the clinical trials reviewed all used the CellSearch™ system for CTCs isolation and reporting. This minireview will focus exclusively on the clinical utility of CTCs as it relates to patient care. We will first review the clinical trial data that validated CTCs ability to predict disease free and overall survival.


Circulating tumor cells in breast cancer: a tool whose time has come of age.

Swaby RF, Cristofanilli M - BMC Med (2011)

(a) Schematic of Cell Tracks CTC separation system and (b) Detection of CTC. a. Epithelial cells are isolated from peripheral blood using antibodies to Ep-CAM conjugated to magnetic particles. Cells are then analyzed to determine the number of CTC. b. Detection of CTC. Two intact CTC are shown in the left panel, 33 damaged CTC in the central panel, and 6 cellular fragments in the right panel.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3107794&req=5

Figure 1: (a) Schematic of Cell Tracks CTC separation system and (b) Detection of CTC. a. Epithelial cells are isolated from peripheral blood using antibodies to Ep-CAM conjugated to magnetic particles. Cells are then analyzed to determine the number of CTC. b. Detection of CTC. Two intact CTC are shown in the left panel, 33 damaged CTC in the central panel, and 6 cellular fragments in the right panel.
Mentions: CTCs are now generally defined as nucleated cells lacking CD45 and expressing cytokeratin [9,10]. Specifically, an antibody to the surface epithelial cell adhesion molecule (epCAM) identifies cells of epithelial origin circulating within the blood. Additionally, cytokeratin antibodies further distinguish CTCs as those that are not white blood cells (i.e. - CD45 negative) and select for carcinomas (i.e. - anti-CK8, anti-CK18, anti-CK19). Although multiple commercially available methods for isolating CTCs exist [11,12], the CellSearch™ system (Veridex Corporation, Warren, NJ) is the only FDA approved system for clinical use with reproducible results across many different laboratories. The CellSearch™ system has been fully described elsewhere [13]; but in summary, the system uses serum enriched for nucleated cells expressing epithelial-cell adhesion molecules, and fluorescently labels them for eventual detection by semi-automated fluorescence-based microscopy. (Figure 1) In this minireview the clinical trials reviewed all used the CellSearch™ system for CTCs isolation and reporting. This minireview will focus exclusively on the clinical utility of CTCs as it relates to patient care. We will first review the clinical trial data that validated CTCs ability to predict disease free and overall survival.

Bottom Line: Circulating tumor cells (CTCs) are isolated tumor cells disseminated from the site of disease in metastatic and/or primary cancers, including breast cancer, that can be identified and measured in the peripheral blood of patients.As recent technical advances have rendered it easier to reproducibly and repeatedly sample this population of cells with a high degree of accuracy, these cells represent an attractive surrogate marker of the site of disease.In this mini-review, we review CTCs in metastatic breast cancer, and discuss their clinical utility for assessing prognosis and monitoring response to therapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. ramona.swaby@fccc.edu

ABSTRACT
Circulating tumor cells (CTCs) are isolated tumor cells disseminated from the site of disease in metastatic and/or primary cancers, including breast cancer, that can be identified and measured in the peripheral blood of patients. As recent technical advances have rendered it easier to reproducibly and repeatedly sample this population of cells with a high degree of accuracy, these cells represent an attractive surrogate marker of the site of disease. Currently, CTCs are being integrated into clinical trial design as a surrogate for phenotypic and genotypic markers in correlation with development of molecularly targeted therapies. As CTCs play a crucial role in tumor dissemination, translational research is implicating CTCs in several biological processes, including epithelial to mesenchymal transition. In this mini-review, we review CTCs in metastatic breast cancer, and discuss their clinical utility for assessing prognosis and monitoring response to therapy. We will also introduce their utility in pharmacodynamic monitoring for rational selection of molecularly targeted therapies and briefly address how they can help elucidate the biology of cancer metastasis.

Show MeSH
Related in: MedlinePlus