Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients

J Clin Oncol. 2005 Oct 20;23(30):7536-45. doi: 10.1200/JCO.2005.03.047. Epub 2005 Sep 12.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / immunology
  • Breast Neoplasms / prevention & control*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / therapeutic use*
  • Disease Progression
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunoconjugates
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control*
  • Peptide Fragments / immunology*
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism
  • T-Lymphocytes, Cytotoxic / metabolism
  • Time Factors


  • Cancer Vaccines
  • HER-2 peptide E75 (369-377), human
  • HLA-A2 Antigen
  • Immunoconjugates
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptor, ErbB-2