Clinical utility of determination of HER-2/neu and EGFR fragments in serum of patients with metastatic breast cancer.
BACKGROUND
The growth factor receptors EGFR and HER-2/neu are targets for new treatment strategies and are of potential use as prognostic and predictive factors. However, the optimal method of determination in order to obtain clinically relevant information remains a source of controversy.


METHODS
HER-2/neu and EGFR expression was examined by immunohistochemistry in primary tumors of patients with breast cancer. In addition, serum was tested for the extracellular domains of HER-2/neu (HER-2/neu ECD) and EGFR (sEGFR) before initiation of therapy for metastatic disease (n=76). The course of disease from the time of metastasis with regard to these parameters was evaluated by univariate and multivariate analyses.


RESULTS
HER-2/neu ECD levels at the time of metastatic disease were correlated with HER-2/neu expression determined by immunohistochemistry from primary tumors (p=0.001). No correlation was observed between expression of EGFR in primary tumors and sEGFR serum levels. HER-2/neu ECD and sEGFR levels at the onset of metastatic disease did not show a significant impact on overall survival.


CONCLUSIONS
Determination of HER-2/neu ECD levels in the serum measured by ELISA at the onset of metastatic disease could offer an alternative to immunohistochemistry of the primary tumor since serum levels are correlated with protein expression in primary tumors. In contrast, no such correlation was observed for EGFR.
Witzel
I
I
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Germany.
Thomssen
C
C
Krenkel
S
S
Wilczak
W
W
Bubenheim
M
M
Pantel
K
K
Neumann
R
R
Jänicke
F
F
Müller
V
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis* / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000097:blood; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases