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.
Highlights
Affecting approximately 200,000 women in the United States alone, breast cancer is recognized to be a heterogeneous disease comprised of several common different phenotypes [1]
Patients with bone metastasis, compared to other sites of disease with ≥5 circulating tumor cells (CTCs) had an additional risk of death. (HR = 1.61; 95% CI 0.52-5.04 [p = 0.410])
Patients who enroll on this study and have elevated CTCs will be randomized to either maintain therapy or switch treatments prior to standard restaging by radiographic assessment (Figure 2)
Summary
Affecting approximately 200,000 women in the United States alone, breast cancer is recognized to be a heterogeneous disease comprised of several common different phenotypes [1]. One hundred and seventy-seven patients with measurable disease had CTCs tested prior to beginning a new palliative treatment regimen for progressive disease, followed by repeat assessment at first follow-up visit approximately 4 weeks later This landmark trial prospectively identified a CTC cut-off level of ≥5 cells per 7.5 ml of blood to be a reliable identifier of patients at higher risk for disease progression and decreased survival from metastatic breast cancer. Additional analysis of CTCs and histologic breast cancer classification and phenotypes in a cohort of 517 MBC patients with either measurable or evaluable disease prior to commencement of new palliative treatment regimens has yielded interesting observations and hypothesis-generating information. A separate retrospective study comparing the predictive capability of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging to CTCs enumeration in a cohort of 115 patients with MBC, again demonstrated CTCs superiority. CTCs response, is most likely an accurate surrogate for radiographic response as well as those with stable disease and this is reflected in the superior clinical outcome associated with low number of
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