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Koenig, Alexander; Vilsmaier, Theresa; Rack, Brigitte; Friese, Klaus; Janni, Wolfgang; Jeschke, Udo; Andergassen, Ulrich; Trapp, Elisabeth; Jückstock, Julia; Jaeger, Bernadette; Alunni-Fabbroni, Marianna; Friedl, Thomas W. P. and Weissenbacher, Tobias (2016): Determination of Interleukin-4,-5,-6,-8 and-13 in Serum of Patients with Breast Cancer Before Treatment and its Correlation to Circulating Tumor Cells. In: Anticancer Research, Vol. 36, No. 6: pp. 3123-3130

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Background/Aim: Circulating tumor cells (CTCs) in women with breast cancer are an indication of prognosis before starting systemic treatment. The aim of this study was the evaluation of cytokine profiles as marker for CTC involvement. Materials and Methods: The analysis of CTCs, the time of blood sampling and the methodology were prospectively designed. There were two groups of patients: 100 women with a positive result for presence of CTCs and 100 women negative for CTCs. These groups were matched into pairs by tumor factors and survival/death. A multi-array ELISA was used to screen T-helper cell (Th) 2 cytokines. The results were analyzed by Spearman correlation coefficient and Mann-Whitney U-test. Results: In patients who were CTC-negative, expression of interleukin-8 (IL-8) and IL-13 was increased (p=0.017 and p=0.045, respectively) if they were negative for progesterone receptor. In patients who died from their tumor, correlation between hormone receptor negativity and an increase in IL-4 was found. IL-5 was increased in patients with lymph node-positive and human epidermal growth factor receptor 2 (HER2)-positive disease (p=0.042). Moreover IL-4 was increased in patients with progesterone receptor-positive and estrogen receptornegative status (p=0.024). Furthermore, the level of IL-6 was increased in patients with tumor grade G3 without progesterone receptor expression. Conclusion: Th2 cytokines are significantly modified in patients who are CTC-negative and progesterone receptor-positive. We suppose that an increase of IL-4 depends on hormone receptor status. In literature, a correlation between IL-4 and resistance to apoptosis is described. We suspect that IL-4 is responsible for the poor outcome of these cases.

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