Science et thérapie du cancer

Breast Cancer Patients Resistant to Endocrine Therapy Show Decreased Number of Cytotoxic Supressor Cells and Enhanced Production of Neoangiogenetic and Immunosupressive Factors

Abstract

Background: Endocrine therapy is an essential modality in patients with hormone receptor positive breast cancer. Even with high therapeutic efficacy of first-line hormonal treatment, most patients with metastatic breast cancer will develop resistance. It appeals, that a factor contributing to the resistance may be a transforming factorbeta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates vascular endotelial growth factor (VEGF). The purpose of the study was to monitor immune responses in patients with hormone receptor positive breast cancer, particularly the examination of cellular (CD4, CD8) as well as humoral immunity, as well as TGF beta and VEGF production. Materials and Methods: Patients included into 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. 12 healthy age matched persons served as control group.TGF beta, VEGF were mesured by ELISA and antitumor cellular immunity (CD4, CD8, antigen presenting cells) was measured by flow cytometry. Results: In patients with resistance to endocrine therapy mainly depression in cellular immunity was found, CD 8, cytotoxic T lymphocytes were significantly [p<0.05] decreased. Immunglobuline plasma level was decreased as well (mainly IgG4 subtype [p<0.05]). 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 significantly increased as compared with healthy person. Conclusion: Correlation of these factors with resistance to endocrine therapy could help in the future with the prediction of therapy response and contribute to the selection of targeted therapy in breast cancer patients. Dedication: This project was supported by govermental grant IGA NT11168-3/2010.