Hla-A2 And Her2 Expression Levels As Clinical Prognostic Factors In Breast Cancer Patients: Implications For Peptide Cancer Vaccine Trials

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Introduction: Our group has been investigating HER2-derived peptide vaccines administered in the adjuvant setting to high risk breast cancer patients (pts) to prevent disease recurrence. Our group has previously shown that pts with HER2 low-expressing (LE) tumors are at higher risk of recurrence than over-expressing (OE) tumors in the trastuzumab era. Given peptide-based cancer vaccination require presentation by a specific HLA molecule, our group has also examined and found comparable disease recurrence rates between HLA-A2+ and HLA-A2- patients. Here, we report recurrence data based on HLA-A2 allele/HER2 expression sub-grouping in our unvaccinated, control pts. Methods: After completing standard of care therapy, high-risk, disease-free breast cancer pts with HER2 LE (IHC 1+, 2+) or OE (IHC 3+) tumors are eligible for enrollment in our 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). Patients are HLA-typed as A2+ or A2- then randomized to vaccine vs. adjuvant alone. Demographics between groups are compared using chi squared or fisher exact. Results: Thus far, 208 pts have been enrolled to the adjuvant alone control arms of the trial. Five pts were excluded from analysis (1 ineligible and 4 second malignancies) for a total of 203 evaluable pts: 88 HLA-A2+ (48 OE and 40 LE) and 115 HLA-A2- (48 OE and 67 LE). A2+ and A2- OE pts exhibited significant difference in respect to age (52 vs. 47, p=0.013) and tumor size (41.7% vs. 68.1% ≥ 2 cm, p=0.01) respectively. With median follow-up of 39 months, recurrence rates were again compared between A2+ vs. A2- pts (11.4% vs. 11.3%, p=0.50) as well as HER2 subgroups (OE, 6.25% vs. LE, 15.8%, p=0.02). The latter difference was particularly prominent among the A2- pts (A2-/OE, 4.2% vs. 16.4%, p=0.03) but less so in the A2+ pts (A2+/OE, 8.3% vs. A2+/LE, 15%, p=0.26). With no recurrence difference between LE A2 subgroups (LE/A2+, 15% vs. LE/A2-, 16.4%, p=0.54), the OE subgroup comparison was notable for 50% increased disease recurrence in A2+ pts (A2+/OE, 8.3% vs. A2-/OE, 4.2%, p=0.33). Conclusions: While there is no difference in recurrence between A2+ and A2- pts overall or among the HER2 LE subset, there does appear to be a difference in the HER2 OE subset. Compared to A2+/OE pts, the A2-/OE pts exhibit 50% decreased disease recurrence despite significantly younger age and larger tumor size. These findings need to be confirmed but are important given that many peptide vaccines target A2+ pts. Therefore, these results may impact future trial design. Citation Format: Erika J. Schneble, Alfred F. Trappey, Timothy J. Vreeland, John S. Berry, Diane F. Hale, Alan K. Sears, Guy T. Clifton, Sathibalan Ponniah, Elizabeth A. Mittendorf, George E. Peoples. HLA-A2 and HER2 expression levels as clinical prognostic factors in breast cancer patients: implications for peptide cancer vaccine trials. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2558. doi:10.1158/1538-7445.AM2014-2558