Cancer Immunology, Immunotherapy

, Volume 57, Issue 12, pp 1817–1825 | Cite as

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

  • Asna Amin
  • Linda C. Benavides
  • Jarrod P. Holmes
  • Jeremy D. Gates
  • Mark G. Carmichael
  • Matthew T. Hueman
  • Elizabeth A. Mittendorf
  • Catherine E. Storrer
  • Yusuf H. Jama
  • Dianna Craig
  • Alex Stojadinovic
  • Sathibalan Ponniah
  • George E. Peoples
Original Article

Abstract

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 (≥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.

Keywords

Vaccine E75 peptide Preventive Recurrence Pathologic patterns Immunologic response 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Asna Amin
    • 1
  • Linda C. Benavides
    • 2
  • Jarrod P. Holmes
    • 3
  • Jeremy D. Gates
    • 2
  • Mark G. Carmichael
    • 4
  • Matthew T. Hueman
    • 4
  • Elizabeth A. Mittendorf
    • 5
  • Catherine E. Storrer
    • 4
  • Yusuf H. Jama
    • 4
  • Dianna Craig
    • 6
  • Alex Stojadinovic
    • 1
  • Sathibalan Ponniah
    • 4
  • George E. Peoples
    • 2
    • 4
  1. 1.Department of SurgeryGeneral Surgery Service, Walter Reed Army Medical CenterWashingtonUSA
  2. 2.Department of SurgeryGeneral Surgery Service, Brooke Army Medical CenterFt. Sam HoustonUSA
  3. 3.Department of Medicine, Division of Hematology and Medical OncologyNaval Medical Center San DiegoSan DiegoUSA
  4. 4.Cancer Vaccine Development Program, Department of SurgeryUnited States Military Cancer Institute, Uniformed Services University of the Health SciencesBethesdaUSA
  5. 5.Surgical Oncology, UTMD Anderson Cancer CenterHoustonUSA
  6. 6.Joyce Murtha Breast Care Center, Windber Medical CenterWindberUSA

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