Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

Cancer Immunol Immunother. 2008 Dec;57(12):1817-25. doi: 10.1007/s00262-008-0509-2. Epub 2008 Apr 8.


Background: E75, a HER2/neu immunogenic peptide, is expressed in breast cancer (BCa). We have performed clinical trials of E75 + GM-CSF vaccine in disease-free, node-positive and node-negative BCa patients at high recurrence risk and recurrences were noted in both control and vaccine groups.

Methods: Among the 186 BCa patients enrolled, 177 completed the study. Patients were HLA typed; the HLA-A2(+)/A3(+) patients were vaccinated; HLA-A2(-)/A3(-) patients were followed as controls. Standard clinicopathological factors, immunologic response to the vaccine, and recurrences were collected and assessed.

Results: The control group recurrence rate was 14.8 and 8.3% in the vaccinated group (P = 0.17). Comparing the 8 vaccinated recurrences (V-R) to the 88 vaccinated nonrecurrent patients (V-NR), the V-R group had higher nodal stage (> or = N2: 75 vs. 5%, P = 0.0001) and higher grade tumors (%grade 3: 88 vs. 31%, P = 0.003). The V-R group did not fail to respond immunologically as noted by equivalent dimer responses and post-DTH responses. Compared to control recurrent patients (C-R), V-R patients trended toward higher-grade tumors and hormone-receptor negativity. C-R patients had 50% bone-only recurrences, compared to V-R patients with no bone-only recurrences (P = 0.05). Lastly, V-R mortality rate was 12.5% compared with 41.7% for the C-R group (P = 0.3).

Conclusions: The vaccinated patients who recurred had more aggressive disease compared to V-NR patients. V-R patients had no difference in immune response to the vaccine either in vitro or in vivo. V-R patients, when compared to C-R patients, trended towards more aggressive disease, decreased recurrence rates, decreased mortality, and no bone-only recurrences.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Dose-Response Relationship, Drug
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • HLA-A3 Antigen / genetics
  • HLA-A3 Antigen / immunology
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Prognosis
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / therapeutic use*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology


  • Adjuvants, Immunologic
  • Cancer Vaccines
  • HLA-A2 Antigen
  • HLA-A3 Antigen
  • Vaccines, Subunit
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptor, ErbB-2