TY - JOUR
T1 - Serum EGFR levels and efficacy of trastuzumab-based therapy in patients with metastatic breast cancer
AU - Hudelist, Gernot
AU - Köstler, Wolfgang J.
AU - Gschwantler-Kaulich, Daphne
AU - Czerwenka, Klaus
AU - Kubista, Ernst
AU - Müller, Ruth
AU - Helmy, Samir
AU - Manavi, Mahmood
AU - Zielinski, Christoph C.
AU - Singer, Christian F.
N1 - Funding Information:
The authors like to thank Dr. Ernst Rücklinger for help with the statistical analysis and Jeff Whittaker for helpful discussions. The resarch project was supported by a grant from Amgen and Ebewe, by a grant from the Jubiläumsfonds der Österreichischen Nationalbank and by the Austrian Federal Ministry for Education, Science and Culture (GZ 200.062/2-VI/1/2002).
PY - 2006/1
Y1 - 2006/1
N2 - The antibody trastuzumab inhibits signal transduction in Her-2/neu overexpressing human breast cancer. However, the activation of co-expressed EGFR has also been show to additionally modulate the anti-tumoural effects of this drug. Similar to Her-2/neu, the extra cellular binding region of EGFR is believed to be proteolytically released from the cell surface upon receptor activation and can be detected in patients' serum (sEGFR). Considering the biological significance of an interaction between EGFR and Her-2/neu signalling in other human malignancies, we have investigated if trastuzumab treatment would affect sEGFR in 33 patients with Her-2/neu overexpressing metastatic breast cancer. We detected EGFR expression in 33% of Her-2/neu overexpressing breast tumours. In contrast to serum Her-2/neu (ECD) levels, which were correlated with the degree of Her-2/neu expression (P = 0.048, Mann-Whitney test), we did not detect significant differences between sEGFR serum levels in EGFR expressing or non-expressing tumours. Furthermore, sEGFR serum levels were not correlated with clinical parameters such as response or clinical benefit rates, and no association was found between increased sEGFR levels and progression-free survival or overall survival. While we have previously observed a selective and significant decrease of ECD levels in patients who derived a clinical benefit from trastuzumab treatment during the first weeks of treatment, we were unable to find similar alterations in sEGFR concentrations. We therefore conclude that the measurement of systemic sEGFR levels in addition to ECD serum concentrations do not allow the prediction of clinical course of trastuzumab-treated patients more accurately.
AB - The antibody trastuzumab inhibits signal transduction in Her-2/neu overexpressing human breast cancer. However, the activation of co-expressed EGFR has also been show to additionally modulate the anti-tumoural effects of this drug. Similar to Her-2/neu, the extra cellular binding region of EGFR is believed to be proteolytically released from the cell surface upon receptor activation and can be detected in patients' serum (sEGFR). Considering the biological significance of an interaction between EGFR and Her-2/neu signalling in other human malignancies, we have investigated if trastuzumab treatment would affect sEGFR in 33 patients with Her-2/neu overexpressing metastatic breast cancer. We detected EGFR expression in 33% of Her-2/neu overexpressing breast tumours. In contrast to serum Her-2/neu (ECD) levels, which were correlated with the degree of Her-2/neu expression (P = 0.048, Mann-Whitney test), we did not detect significant differences between sEGFR serum levels in EGFR expressing or non-expressing tumours. Furthermore, sEGFR serum levels were not correlated with clinical parameters such as response or clinical benefit rates, and no association was found between increased sEGFR levels and progression-free survival or overall survival. While we have previously observed a selective and significant decrease of ECD levels in patients who derived a clinical benefit from trastuzumab treatment during the first weeks of treatment, we were unable to find similar alterations in sEGFR concentrations. We therefore conclude that the measurement of systemic sEGFR levels in addition to ECD serum concentrations do not allow the prediction of clinical course of trastuzumab-treated patients more accurately.
KW - EGFR (activation) serum levels
KW - Her-2/neu
KW - Trastuzumab efficacy
UR - http://www.scopus.com/inward/record.url?scp=30544438325&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2005.08.036
DO - 10.1016/j.ejca.2005.08.036
M3 - Article
C2 - 16326100
AN - SCOPUS:30544438325
SN - 0959-8049
VL - 42
SP - 186
EP - 192
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 2
ER -
