Background: We are conducting a Phase II clinical trial of the AE37+GM-CSF vaccine for the prevention of breast cancer recurrence in disease-free, node-positive or high-risk node negative patients (pts). AE37, is an MHC Class II epitope capable of stimulating CD4+ helper T cells. Here, we present the final pre-specified analysis of the primary endpoint of disease free survival (DFS) at one year from last enrolled pt. Methods: After completion of standard of care therapy, pts with any level of HER2 expression (IHC1-3+) were randomized to the vaccine group (VG) to receive 6 monthly intradermal inoculations of AE37+GM-CSF followed by 4 booster vaccinations every 6 months, or to receive GM-CSF alone on the same schedule as a control group(CG). Demographic, safety, immunologic, and clinical recurrence data are being collected. DFS is compared using Kaplan-Meir methods (5 yr DFS rates and logrank test) and Cox proportional hazards models (HR estimates with 95% CI). Continuous variables are compared using analysis of variance techniques and proportions compared with Fisher’s exact test. Results: Of 301 enrolled pts, 154 were randomized to the VG and 147 to the CG. There were no differences in age, grade, receptor status, tumor size or nodal status between groups (all p ≥ 0.1). Five-year DFS rates were not different with 82% (VG) vs 79.9% (CG), HR = 0.96, p = 0.9. There were trends in several subgroups. In HER2 1-2+ pts (77 VG vs 80 CG), 5 yr DFS was 79% (VG) vs 75% (CG), HR 0.76, p = 0.48. In ER/PR- pts (59 VG vs 56 CG), 5 yr DFS was 83% (VG) vs 77% (CG), HR 0.67, p = 0.36. In TNBC pts (25 VG vs 26 CG), 5 yr DFS was 67% (VG) vs 62% (CG), HR 0.65, p = 0.42. Conclusions: Overall, the final timed analysis of this phase II trial shows no statistical differences between treatment arms; however, it does identify particular pt populations where the vaccine may have efficacy. The ER/PR negative and triple negative pts appear to derive greatest benefit from AE37 vaccination with reductions in relative risk of recurrence of 33% and 35%, respectively. Further studies are required to confirm these findings and investigate the link between hormone receptor status and induction of clinically beneficial anti-tumor immunity by the AE37 vaccine. Clinical trial information: NCT00524277