Incidence of hormone-receptor negative and basal type breast tumors among HLA-A2+ patients and possible implications for cancer vaccine trials: U.S. Military Cancer Institute clinical trials group study I-01, I-02, I-03, and I-04.

Abstract

Abstract Abstract #3153 Background: Breast cancer prognosis is significantly impacted by expression levels of steroid hormone receptors for estrogen (ER) and progesterone (PR), as well as HER2/neu, a member of the epidermal growth factor receptor family of tyrosine kinases. Recent advances in molecular typing of breast tumors have defined a poor risk subtype of tumor called basal cell. These basal cell breast tumors are “triple negative,” meaning ER and PR negative, and none to low HER2/neu expression (immunohistochemistry [IHC] 0, 1+, or 2+ tumors). Basal cell tumors have a poorer prognosis and do not respond to conventional hormonal or targeted therapy aimed at HER2/neu overexpressing tumors (IHC 3+). Our Cancer Vaccine Development Program (CVDP) has performed several phase I and II clinical trials using immunogenic peptides from the HER2 protein to include E75, GP2, and AE37. Here we present data analysis of ER, PR, and basal cell tumors in HLA-A2+ and A2- patients. Methods: Vaccine trials utilizing E75, GP2, and AE37 were performed separately with similar designs targeting patients with all levels of HER2 expression (IHC 1-3+). Upon completion of standard breast cancer therapy and prior to HLA-typing, disease-free patients were enrolled in the various vaccine trials. HLA-A2 status was determined via flow cytometry of peripheral blood mononuclear cells as E75 and GP2 are HLA-A2+ restricted whereas AE37 is a promiscuous HLA Class II binder. Standard demographic data (including ER, PR and HER2/neu status) were collected, and patients vaccinated according to their respective trial protocol. Data from all trials were pooled for this analysis. Results: To date, of 254 patients enrolled in the trials 54.3% (n=138) were HLA-A2+. Age, tumor size and nodal status were similar between the A2+ and A2- patients. Significantly more A2+ patients had hormone receptor negative (ER-PR-) tumors (n=49) compared to A2- patients (n=27) (35.5% vs. 23.3%; p= 0.03). There was a trend towards increased basal cell tumors among A2+ patients compared to A2- (15.2% vs. 9.5%; p=0.17). Conclusions: Across these clinical trials conducted by the CVDP, HLA-A2+ patients have an increased incidence of ER-PR- tumors and trend toward increased basal cell tumors. ER-PR- and basal cell tumors have a worse prognosis and fewer treatment options than ER+PR+ tumors. As previously reorted, peptide vaccines targeting the HER2/neu protein are safe and effective in eliciting an immune response in patients with tumors expressing various levels of HER2/neu,to include the low levels associated with basal cell tumors. Therefore, peptide cancer vaccines may provide an excellent adjunctive to current treatment for basal cell tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3153.