title: Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.
abstract: OBJECTIVE
  E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients.
  
  
  METHODS
  E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented.
  
  
  RESULTS
  One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted.
  
  
  CONCLUSIONS
  E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.
authors.affiliation: Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas 78234, USA. george.peoples@amedd.army.mil
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
authors.forename: Jarrod P
authors.initials: JP
authors.lastname: Holmes
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Hueman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
authors.forename: Asna
authors.initials: A
authors.lastname: Amin
authors.forename: Steven
authors.initials: S
authors.lastname: Khoo
authors.forename: Zia A
authors.initials: ZA
authors.lastname: Dehqanzada
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Gurney
authors.forename: Michael 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: Dianna
authors.initials: D
authors.lastname: Craig
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Ioannides
authors.forename: Sathibalan
authors.initials: S
authors.lastname: Ponniah
mesh_terms: D017304:Annexin A5 / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology* / Q000517:prevention & control; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D015789:HLA-A2 Antigen / Q000097:blood; D015791:HLA-A3 Antigen / Q000097:blood; D006801:Humans; D008887:Military Medicine; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D012449:Safety; D014481:United States
chemical_list: D017304:Annexin A5; D019496:Cancer Vaccines; D017931:DNA Primers; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases