Abstract 5382: Vascular endotelial growth factor and transforming growth factor-beta are enhanced in plasma of breast cancer patients resistant to endocrine therapy

Abstract

Abstract Although more than 2/3 of treated patients respond to the endocrine therapy, most patients with metastatic breast cancer will develop resistance. Estrogen modulate angiogenesis, in part, through the effects on VEGF. It appears that other factor contributing to the resistance may be a transforming 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: 60 patients included in the research project were implemented routine cancer teratment 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, VEGF were mesured by ELISA and anti-tumor 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 dicreased 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/anti phospholipide and anti cardiolipin 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 hotmonal therapy and contribute to the selection of targeted immune therapy in cancer patients. Dedication: This project was supported by grant IGA NT11168-3/2010 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5382. doi:1538-7445.AM2012-5382