Search

Background: Metastatic breast cancer (MBC) is generally considered to be incurable. Although many options are available for treating MBC, physicians often encounter difficulties in choosing the most appropriate treatment because the MBCs of individual patients respond differently even to the same treatments. Thus, predictive markers for therapeutic efficacy are urgently needed. Neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR, respectively), have been studied and established as prognostic markers for breast cancer patients but whether either or both of these markers are predictive of treatment responses is still unclear. Herein, we investigated predictive markers for eribulin-based treatment responsiveness in patients with MBC, by examining clinicopathological features, including several markers of immunocompetent cells in peripheral blood., Methods: Clinicopathological features of the 104 patients with metastatic/Stage IV breast cancer given eribulin-based regimens were investigated in relation to clinical responses to eribulin-based treatments and progression-free-survival (PFS)., Results: Special histological types and high NLR at baseline were independently related to poor clinical responses to the treatments (p = 0.023 and 0.039, respectively). The Cox hazard model revealed that patients with oestrogen receptor (ER)-negative tumours and high NLR, monocyte-to-lymphocyte ratio (MLR) and PLR showed significantly shorter PFS (p = 0.021, 0.005, 0.008 and 0.030, respectively). On multivariate analysis, only ER status and NLR remained independent factors related to PFS (p = 0.011 and 0.003, respectively)., Conclusions: Our data revealed that special histological types and high NLR might be factors related to low responsiveness to eribulin-based regimens in patients with MBC.

Several clinical studies have examined circulating tumour cells (CTCs). However, the application of CTCs as a predictive/prognostic marker for breast cancer patients has yet to be established, particularly the selection of suitable markers for detecting CTCs. We recently investigated CTCs, including mesenchymal status, from metastatic breast cancer patients who had received eribulin-based treatment. We found that assessment of both mesenchymal and epithelial CTCs might be important for predicting eribulin responsiveness. In the current study, we followed up the outcomes of these patients after eribulin treatment and investigated the possibility of CTC analysis results serving as prognostic markers for this patient population. Twenty-one patients were enrolled and peripheral blood samples were collected before eribulin-based treatments. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Overall survival (OS) was assessed in relation to the number of CTCs and clinicopathological factors. During the observation period, 13 patients (62%) died due to breast cancer and the median OS was 18 months. Patients with high-grade tumours and a high total number of CTCs showed significantly shorter OS than those with low-grade tumours and smaller CTC burdens (p = 0.026 and 0.037, respectively). Patients who received eribulin as the first chemotherapy for metastatic disease showed longer OS (p = 0.006). Our data suggest that determining numbers of both mesenchymal and epithelial CTCs might predict survival for patients receiving eribulin.

Background: Liquid 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., Methods: Twenty-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., Results: Numbers 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)., Conclusions: Our 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).