Abstract C68: Transforming growth factor-beta and vascular endothelial growth factor are enhanced in plasma of breast cancer patients resistent to hormone therapy

Abstract

Abstract Even with high therapeutic efficacy of first-line hormonal treatment, most patients with metastatic breast cancer will develop resistance. It appears that a factor contributing to the resistance may be a transforming growth factor-beta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates production of vascular endotelial growth factor (VEGF). Defects in the immune response correlated with poor prognosis and therefore in recent years, research focused on a precise description of the status and function of the immune system and its possible effect in cancer patients. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer resistant to hormone therapy, particularly the examination of cellular (CD4, CD8, HLA-DR) as well as humoral immunity. TGF-beta and VEGF production was monitored and we analyzed the changes during hormonal treatment. Methods: Patients included in the research project were implemented routine cancer treatment with hormonal therapy. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF-beta and VEGF were mesured by ELISA and antitumor cellular immunity (CD4, CD8, antigen presenting cells) will be measured by flow cytometry. Results: In patients with resistance to hormone therapy mainly depression in cellular immunity was found. Immunglobulin plasma level was decreased as well (mainly IgG4 subtype). Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections) TGF-beta as well as VEGF plasma level were increased. Significant increase of autoantibodies production was found, particulary in those, involved into blood coagulacion process/antiphospholipide and anticardiolipin autoantibodies. Conclusion: Correlation of these factors with resistance to hormonal therapy, and the state of anticancer immunity could help in the future with the the prediction of resistance to hormonal therapy and contribute to the selection of targeted immune therapy in cancer patients. Acknowledgement: This project was supported by grant IGA NT11168-3/2010. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C68.