Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/neu-specific immunity

We questioned whether the incidence or magnitude of the humoral or cellular immune response to the self-tumor antigen HER-2/ neu is influenced by the level of HER-2/ neu protein overexpression as defined by immunohistochemical staining of tumors in breast cancer patients. We obtained peripheral blood from 104 women with stage II, III, and IV pathologically confirmed HER-2/ neu -overexpressing breast cancer. Patients were categorized with +1 ( n = 14), +2 ( n = 20), or +3 ( n = 70) HER-2/ neu overexpression by institutional pathologic report. Circulating antibodies to HER-2/ neu were evaluated using ELISA. T-cell responses to HER-2/ neu were measured using an antigen-specific tritiated thymidine incorporation assay. Eighty-two percent of subjects with HER-2/ neu antibodies were +3 overexpressors compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly significant difference ( P < 0.001), and there were significant differences in the magnitude of the HER-2/ neu -specific antibodies between groups with varying HER-2/ neu protein expression ( P = 0.022). In addition, 65% of subjects with HER-2/ neu -specific T cells were +3 overexpressors compared with 16% +2 overexpressors and 19% +1 overexpressors ( P = 0.001). Data presented here indicate that endogenous HER-2/ neu -specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/ neu expression. Overexpression of a self-tumor-associated protein is a potential mechanism by which immunogenicity is enhanced and may aid in the identification of biologically relevant proteins to target for immune-based molecular cancer therapies. [Mol Cancer Ther 2008;7(3):449–54]