title: Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Breast Care Project, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA. george.peoples@na.amedd.army.mil
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Gurney
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Hueman
authors.forename: Mike M
authors.initials: MM
authors.lastname: Woll
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Ryan
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Storrer
authors.forename: Christine
authors.initials: C
authors.lastname: Fisher
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Ioannides
authors.forename: Sathibalan
authors.initials: S
authors.lastname: Ponniah
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015789:HLA-A2 Antigen; D018796:Immunoconjugates; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C474513:HER-2 peptide E75 (369-377), human