Abstract P4-13-05: HLA-A2 is not a prognostic indicator in breast cancer: Implications for cancer vaccine trials
Authors: Trappey AF , Berry JS , Vreeland TJ , Guy CT , Diane HF , Alan SK , Erika SJ , Ferrise L , Shumway NM , Papamichail M , Perez SA , Ponniah S , Mittendorf EA , Peoples GE 
Published: August 2014

Abstract
Introduction
Peptide-based cancer vaccines require presentation by a specific HLA molecule. HLA-A2 is the most common class I allele in the US (40-50% of the population) and, therefore, the most commonly targeted. Our group has been investigating HER2-derived peptide vaccines administered in the adjuvant setting to high risk breast cancer patients in order to prevent disease recurrence. This study was undertaken to compare known prognostic factors and disease-free survival (DFS) in control HLA-A2+ and HLA-A2- patients in order to better define these populations for future trial design.
Methods
Our group is currently enrolling patients in a phase II trial evaluating the HER2-derived peptide vaccines, AE37 (MHC Class II, HLA-non-restricted epitope) and GP2 (MHC Class I, HLA-A2+ restricted epitope). The studies are enrolling high-risk, disease-free breast cancer patients with any level of HER2 expression (IHC 1+, 2+ or 3+) after completion of standard of care therapy. Patients are HLA-typed. HLA-A2+ patients are randomized to GP2+GM-CSF or GM-CSF alone. HLA-A2- patients are randomized to AE37+GM-CSF or GM-CSF alone. Demographics between groups are compared using chi squared or fisher exact as appropriate. DFS is compared using log rank.
Results
Thus far, 407 patients have been enrolled to the study (181 HLA-A2+ and 226 HLA-A2-). Demographics are shown in Table 1.
Table 1. Demographics (all) A2+A2-pn181226 Age (median)51500.47Node Positive62%66%0.46Grade 354%54%0.99Tumor &gt;/ = 2 cm59%64%0.23ER/PR Negative36%38%0.59HER2 Overexpression55%51%0.39Triple Negative13%15%0.52
There are no differences between groups with respect to age, node positivity, grade, tumor size, ER/PR status, HER2 over-expression, or triple negative breast cancer. Of those enrolled, 83 HLA-A2+ patients and 109 HLA-A2- patients have been randomized to the control groups. Within the control group, there are no differences between the HLA-A2+ and HLA-A2- patients regarding age, node positivity, grade, tumor size, ER/PR status, HER2 over-expression, or triple negative breast cancer (Table 2).
With a median follow-up of 30 months, DFS is similar between A2+ and A2- control patients (83% v. 80%, p = 0.93).
Conclusions
Baseline clinico-pathologic factors are similar between HLA-A2+ and HLA-A2- breast cancer patients with no correlations to known prognostic factors. Well-matched blinded control patients treated only with GM-CSF demonstrate no differences in DFS between HLA-A2+ and HLA-A2- patients. Therefore, it does not appear that HLA-A2 status is a prognostic factor in breast cancer, and HLA-A2+ and HLA-A2- patients should be comparable in peptide-based breast cancer vaccine trials.
Table 2. Demographics (Control Group Only) A2+A2-pn83109 Age (median)51510.75Node Positive65%64%0.99Grade 359%57%0.76Tumor &gt;/ =59%71%0.08ER/PR Negative36%38%0.84HER2 Overexpression55%46%0.19Triple Negative11%16%0.34
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-13-05.