High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer.
OBJECTIVE
To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor.


METHODS
The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population.


RESULTS
The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of > or = 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (0%) normal controls (P < .01). The presence of antibodies to HER-2/neu also correlated to overexpression of HER-2/neu protein in the patient's primary tumor. Nine of 44 (20%) patients with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, whereas three of 63 (5%) patients with HER-2/neu-negative tumors had antibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%).


CONCLUSIONS
The presence of HER-2/neu antibodies in breast cancer patients and the correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu protein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic proteins as tumor markers, as well as the development and testing of vaccine strategies to induce and augment immunity to HER-2/neu for the treatment of breast cancer or prevention of recurrent disease.
Disis
M L
ML
Department of Medicine, University of Washington, Seattle 98195-6527, USA. ndisis@u.washington.edu
Pupa
S M
SM
Gralow
J R
JR
Dittadi
R
R
Menard
S
S
Cheever
M A
MA
D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000912:Antibodies, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases