Chemosensitivity Testing of Circulating Epithelial Cells (CETC) in Breast Cancer Patients and Correlation to Clinical Outcome.

Abstract

In spite of ample prognostic markers available in breast cancer, still a considerable proportion of patients with good prognostic markers suffers relapse whereas patients with poor prognostic markers may remain disease free. It would, therefore, be desirable to control, at the individual patient level, whether the applied therapy is effective. Our previous work indicates, that in cancer patients most of the epithelial cells circulating in peripheral blood (CETC) are part of the tumor and that the response of these cells reflects the response of the tumor to the applied therapies.Therefore, these cells were used to assay chemosensitivity in short time cultures analyzing the percent of cell killing during short time incubation and monitoring the decrease or increase in numbers of these cells during treatment with the respective agents providing a unique tool for therapy surveillance. Patients were prospectively analysed for the number of CETC before each new combination of chemotherapy. 1ml of blood was drawn into EDTA vials, red blood cells lysed and the white blood cell pellet stained with FITC-labelled anti-Epcam. Green fluorescent cells were detected by image analysis and dead cells excluded due to red PI fluorescence. Activity of individual compounds was determined using three different concentrations of each compound at 3h, 6h and 12hs and displayed as % cell killing. The in vitro results were then compared to in vivo reduction of CETCs and to the reduction of a marker lesion.215 patients have been investigated so far. Cell killing was dose and time dependent. The highest killing rates were observed with Epirubicin and Taxanes, agents which are known for their high activity in breast cancer. Less than 20% killing activity was termed marginal activity. In vitro sensitivitity was highly significantly predictive of in vivo CETC reduction. In some cases an increasing resistance could be shown to develop during repeated cycles of the same combination therapy. CETC reduction was correlated with a prolonged progression free survival.Thus this approach can in the future be used to test in advance the sensitivity of the circulating tumor cells to chemotherapy and at the same time monitor the current response of the cells to therapy in vivo in order to optimize and individualize therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2044.

Exploration of disease - specific biomarkers in cancer research by integrating biological knowledge and high throughput data

“…Due to their involvement in the metastasis CTCs can indeed play an important role in the treatment of the cancer [Lianidou, 2014]. We can even potentially use them for testing the efficacy of existing tumour therapies like chemotherapy at the individualized level ("chemosensitivity") [Pachmann et al, 2014]. But first we need to find ways to detect CTCs in the blood of the patients, which is quite challenging in practice.…”