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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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Schematic of SWOG SO500. A randomized phase III trial to test the strategy of changing therapy vs maintaining therapy for Metastatic Breast Cancer patients who have elevated circulating tumor cell levels at first follow-up assessment.
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Figure 2: Schematic of SWOG SO500. A randomized phase III trial to test the strategy of changing therapy vs maintaining therapy for Metastatic Breast Cancer patients who have elevated circulating tumor cell levels at first follow-up assessment.

Mentions: HER-2 amplification by fluorescent in situ hybridization (FISH) has been detected in CTCs, both concordant and discordant with the primary tumor phenotypic analysis. Interestingly, trastuzumab based therapy was administered to 4 of 9 patients with MBC in whom HER-2 positive CTC cells were detected, despite the primary site testing HER-2 negative by standard pathology techniques. Three of those four patients responded - one experiencing a complete response and two experiencing partial responses. This modest sample validates the hypothesis that the most relevant tumor cell population is the one that has proven ability to disseminate through the blood stream and may be the most representative population of metastatic disease [35]. Additionally, the possibility of collecting sequential blood samples for real-time monitoring of the efficacy of systemic therapies offers new possibilities to evaluate targeted therapies based on genomic profiling of CTCs and to improve the clinical management of patients with advanced disease [35-37]. This strategy is currently undergoing its first, large prospective, randomized validation study [38]. Patients who enroll on this study and have elevated CTCs will be randomized to either maintain therapy or switch treatments prior to standard re-staging by radiographic assessment (Figure 2).


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

Swaby RF, Cristofanilli M - BMC Med (2011)

Schematic of SWOG SO500. A randomized phase III trial to test the strategy of changing therapy vs maintaining therapy for Metastatic Breast Cancer patients who have elevated circulating tumor cell levels at first follow-up assessment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Schematic of SWOG SO500. A randomized phase III trial to test the strategy of changing therapy vs maintaining therapy for Metastatic Breast Cancer patients who have elevated circulating tumor cell levels at first follow-up assessment.
Mentions: HER-2 amplification by fluorescent in situ hybridization (FISH) has been detected in CTCs, both concordant and discordant with the primary tumor phenotypic analysis. Interestingly, trastuzumab based therapy was administered to 4 of 9 patients with MBC in whom HER-2 positive CTC cells were detected, despite the primary site testing HER-2 negative by standard pathology techniques. Three of those four patients responded - one experiencing a complete response and two experiencing partial responses. This modest sample validates the hypothesis that the most relevant tumor cell population is the one that has proven ability to disseminate through the blood stream and may be the most representative population of metastatic disease [35]. Additionally, the possibility of collecting sequential blood samples for real-time monitoring of the efficacy of systemic therapies offers new possibilities to evaluate targeted therapies based on genomic profiling of CTCs and to improve the clinical management of patients with advanced disease [35-37]. This strategy is currently undergoing its first, large prospective, randomized validation study [38]. Patients who enroll on this study and have elevated CTCs will be randomized to either maintain therapy or switch treatments prior to standard re-staging by radiographic assessment (Figure 2).

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