Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study.

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).

Cardiotoxicity after Additional Administration of Pertuzumab following Long-Term Trastuzumab: Report of 2 Cases.

Pertuzumab, a humanized antibody drug, has improved outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, when administered in combination with trastuzumab and other chemotherapies. Cardiotoxicity due to trastuzumab is widely recognized, while data on pertuzumab-based treatments in daily clinical practice are lacking. We herein report 2 Japanese patients, aged 72 and 49 years, who developed left ventricular dysfunction after pertuzumab administration, following long-term trastuzumab treatments. Both patients underwent curative surgery for their HER2-positive breast cancer and received anthracycline-based treatments. After developing metastatic disease, trastuzumab-based treatments were administered without cardiac toxicity, but both patients developed left ventricular dysfunction after pertuzumab administration (6 and 13 cycles, respectively). Although several large randomized trials have shown no additive effect of pertuzumab on cardiac dysfunction, careful monitoring of cardiac function appears to be necessary in daily practice, particularly for patients with prior long-term trastuzumab treatments.

Impact of circulating tumour cells on survival of eribulin-treated patients with metastatic breast cancer.

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.

Full-dose capecitabine with local radiotherapy: one of the treatment options for inoperable T4 breast cancer.

A 48-year-old woman presented with a 15-cm diameter tumor in her left breast with fixation to the chest wall and palpable axillary lymph nodes. Pathology study showed pure-type mucinous carcinoma. Pretreatment staging investigations showed multiple lung metastases, which resulted in the diagnosis of T4N2M1 breast cancer. Four cycles of cyclophosphamide 700 mg/m(2)/epirubicin 70 mg/m(2) (CE) were performed initially, but the tumors decreased only within the treatment response criteria of stable disease (SD). The second regimen of docetaxel could not continue due to drug allergy. Two more cycles of CE did not improve the situation. Then, treatment was continued with full-dose capecitabine with local radiotherapy. She received radiotherapy to the left breast and axillary region with 60 Gy/30 fractions/6 weeks and concomitant capecitabine 2400 mg/body twice daily for 21 days; the cycles were repeated every 28 days. After radiotherapy, tumors decreased in size, and the skin ulceration disappeared. She continued to receive capecitabine on the same schedule. She now has no palpable tumor in her left breast and no tumor in the axilla or lung on CT. She is alive and well 6 years after radiotherapy.