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

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.

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.

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.