Prognostic significance of HLA-A2 status in breast cancer patients

Abstract

9702 Background: HER2/neu (HER2) is a known prognostic factor in breast cancer and has been targeted by peptide vaccines. HLA-A2 (A2) is present in 40–50% of Caucasians. We are testing an A2-binding, HER2 peptide, E75, vaccine in node-positive (NP) and node-negative (NN) breast cancer patients. We have observed differences in known prognostic factors in these patients based on A2 status. Therefore, we have combined data from both trials to determine the prognostic significance of the A2 status. Methods: We have enrolled 98 patients into the NN (n=46) and NP (n=52) trials evaluating the E75 vaccine to induce HER2 immunity and prevent recurrence. Patients are enrolled and then HLA typed; clinical parameters should be evenly distributed. A2+ patients (n=46) have been vaccinated, and A2- patients (n=52) have been followed as controls. All pertinent clinical prognostic factors have been documented. Since the trial design is preventive, no requirement for HER2 over-expression exists. HER2 varied from 0–3+ (IHC). Patients can be categorized: A2-/HER2- (n=22), A2+/HER2- (n=19), A2-/HER2+ (n=28), and A2+/HER2+ (n=24). Results: Taken collectively, A2+ patients have fewer +ve nodes compared to A2- patients (mean=1.96 vs 2.69, p<0.3) despite having larger tumors (≥2 cm, 41% vs 33%), higher grade (grade 3, 41% vs 28%, p<0.17), and more ER-/PR- cancers (24% vs 15%), respectively. When assessed by HER2 status, differences are more apparent. If HER2-, the proportion of patients with +ve nodes is similar (36% vs 37%) between the A2- and A2+ groups; however, the median (range) number of +ve nodes is 4.5 (1–11) compared to 1 (1–5), respectively (p<0.15). If HER2+, 78% of the A2- patients are node +ve compared to only 67% of the A2+ (p<0.3) suggesting a trend related to A2 status. This trend is even more apparent in the HER2 3+ patients (n=24) with 92% of A2- patients being node +ve compared to 58% of A2+ patients (p<0.059). Conclusions: HLA-A2 appears protective in some breast cancer patients with A2+ patients developing more aggressive cancers prior to nodal metastasis. This protection is most apparent among HER2+ patients, particularly with HER2 over-expression. If confirmed in larger studies, these findings may have implications for risk assessment in breast cancer patients. No significant financial relationships to disclose.