Originally published as JCO Early Release 10.1200/JCO.2005.03.047 on September 12 2005

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Clinical Trial Results of a HER2/neu (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients

From the Clinical Breast Care Project, Walter Reed Army Medical Center, Washington, DC; Uniformed Services, University of the Health Sciences, Bethesda, MD; and the University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to George E. Peoples, MD, Department of Surgery, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Washington, DC 20307-5001; e-mail: george.peoples{at}na.amedd.army.mil

PURPOSE: E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC).

PATIENTS AND METHODS: Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2⁺ patients (n = 24) were vaccinated, and HLA-A2^– patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured.

RESULTS: Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8⁺T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P < .01). HLA-A2⁺ patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2^– patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P < .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response.

CONCLUSION: This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.

Supported by the Clinical Breast Care Project, a Congressionally funded program of the Henry M. Jackson Foundation for the Advancement of Military Medicine (Rockville, MD). Supported by the United States Army Medical Research and Materiel Command and the Department of Clinical Investigation at the Walter Reed Army Medical Center.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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