Abstract
BackgroundLiquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy.MethodsTwenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs.ResultsNumbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively).ConclusionsOur data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM).
Highlights
Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies
Results mesenchymal circulating tumour cells (mCTCs) were frequently observed in patients with triple negative (TN) metastatic breast cancer (MBC) CTCs were detected in 21 of 22 patients
When the patients were categorised into two groups, partial response (PR)/stable disease (SD) and progressive disease (PD), total and mCTC were higher in the PD group, the differences were not statistically significant (Fig. 3a)
Summary
Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. CTC analysis in breast cancer research Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs) and DNA, have recently been introduced in clinical studies on a broad range of cancer types. Improvement of technology in CTC analysis The CellSearch® System has become the most widely used technique for CTC analysis in both pre-clinical and clinical studies [7] This system captures CTCs using antibodies against epithelial cellular adhesion molecule (EpCAM) and several epithelial cell surface markers, including CK8, 18 and 19. A subpopulation of CTCs with decreased levels of epithelial markers might escape from EpCAM-based detection [8] and epithelial-to-mesenchymal transition (EMT) and could thereby be a major reason for this phenomenon [6, 8, 11,12,13,14,15]
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