The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.
OBJECTIVE
HER2/neu, a source of immunogenic peptides, is expressed in >75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed.


METHODS
Patients were stratified by HER2/neu expression. Low expressors (n = 100) were defined as HER2/neu immunohistochemistry (IHC) 1(+) to 2(+) or fluorescence in situ hybridization < 2.0. Overexpressors (n = 51) were defined as IHC 3(+) or fluorescence in situ hybridization > or = 2.0. Additional analyses were done stratifying by IHC status (0-3(+)). Standard clinocopathlogic factors, immunologic response (in vivo delayed-type hypersensitivity reactions; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay), and clinical responses (recurrence; mortality) were assessed.


RESULTS
Low-expressor (control, 44; vaccinated, 56) versus overexpressor patients (control, 22; vaccinated, 29) were assessed. Low expressors, overexpressors, and most IHC-status vaccinated groups responded immunologically. Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients (P = 0.04), and vaccinated IHC 1(+) patients had increased long-term immune response (P = 0.08). More importantly, compared with controls, low-expressor patients had a mortality reduction (P = 0.08). The largest decrease in mortality was seen in IHC 1(+) patients (P = 0.05). In addition, a subset of overexpressor patients (n = 7) received trastuzumab before vaccination, and this combination seems safe and immunologically beneficial.


CONCLUSIONS
Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination. The low expressors, specifically IHC 1(+) patients, had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine.
Benavides
Linda C
LC
Department of Surgery, General Surgery Service, Brooke Army Medical Center, Houston, Texas 78234, USA.
Gates
Jeremy D
JD
Carmichael
Mark G
MG
Patil
Ritesh
R
Patel
Ritesh
R
Holmes
Jarrod P
JP
Hueman
Matthew T
MT
Mittendorf
Elizabeth A
EA
Craig
Dianna
D
Stojadinovic
Alexander
A
Ponniah
Sathibalan
S
Peoples
George E
GE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000401:mortality / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000276:immunology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019496:Cancer Vaccines; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C474513:HER-2 peptide E75 (369-377), human