Purpose: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. Experimental Design: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. Results: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. Conclusions: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.Breast cancer is the most common cancer diagnosis in women and the second leading cause of cancer-related death among women.7 Despite advances in standard treatment, a significant proportion of breast cancer patients will ultimately die from recurrent disease, especially aggressive subsets, such as those overexpressing HER2/neu. HER2/neu is a protooncogene expressed in many epithelial malignancies (1). Overexpression of HER2/neu is found in 20% to 25% of breast cancer and confers a poor prognosis (2).Novel approaches are needed to further improve outcomes among breast cancer patients, and one such approach is immunotherapy. Trastuzumab is a monoclonal antibody that targets the HER2/neu protein and is an effective treatment of metastatic breast cancer (3). Several recent large trials have shown that adjuvant trastuzumab decreases recurrence rates compared with chemotherapy alone (4 -6).Another mode of immunotherapy in treating cancer is vaccines. Tumor-associated antigens are proteins expressed by 7 Ries LAG, Harkins D, Krapcho M, et al. (eds.).

The hybrid AE37 vaccine seems safe and well tolerated with minimal toxicity if properly dosed. AE37 is capable of eliciting HER-2/neu-specific immune responses, even without the use of an adjuvant. This trial represents the first human experience with the Ii-Key modification, and to our knowledge, AE37 is the first peptide vaccine to show potency in the absence of an immunoadjuvant.