Article (Scientific journals)
Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC).
Giuliani, Rosa; Durbecq, Virginie; Di Leo, Angelo et al.
2007In European Journal of Cancer, 43 (4), p. 725-35
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Keywords :
Antibodies, Monoclonal/therapeutic use; Antineoplastic Agents/therapeutic use; Breast Neoplasms/drug therapy/genetics; Female; Gene Amplification; Genes, erbB-2/genetics; Humans; In Situ Hybridization, Fluorescence; Neoplasm Metastasis; Phosphorylation; Protein-Tyrosine Kinases/genetics/metabolism; Receptor, erbB-2/metabolism; Retrospective Studies; Treatment Outcome
Abstract :
[en] AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional predictive markers. The following markers could be implicated in response to T: (1) the magnitude of Her-2 gene amplification; (2) the co-expression of the other HER family receptors, possibly responsible for HER-2 trans-activation; (3) the activated status of HER-2; (4) the activated status of downstream effectors as mitogen-activated protein kinases (MAPKs), p38 and p27. METHODS: Medical files of patients with MBC treated with T either as a single agent or in combination with chemotherapy (CT) were reviewed. HER family members (EGFR, HER-2, HER-3, HER-4), the phosphorylated forms of EGFR (p-EGFR), HER-2 (p-HER-2) and of the downstream effectors were evaluated in the archival tumours. The correlation between clinical outcome and the expression of these markers was investigated. RESULTS: (1) Increasing values of Her-2 amplification were associated with a higher probability of achieving an objective response; (2) no statistical significant correlation between the expression of the HER family receptors was found; (3) p-HER-2 was predictive of response in patients treated with T+CT; (4) a statistically significant correlation between p-ERK 1/2, p-p38 and p-HER-2 emerged, pointing to the activated vertical pathway p-HER-2-->p-MAPKs. CONCLUSIONS: p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials.
Disciplines :
Oncology
Author, co-author :
Giuliani, Rosa
Durbecq, Virginie
Di Leo, Angelo
Paesmans, Marianne
Larsimont, Denis
Leroy, Jean-Yves
Borms, Marleen
Vindevoghel, Anita
Jerusalem, Guy  ;  Centre Hospitalier Universitaire de Liège - CHU > Oncologie médicale
D'Hondt, Veronique
Dirix, Luc
Canon, Jean-Luc
Richard, Vincent
Cocquyt, Veronique
Majois, Françoise
Reginster, Michel
Demol, Jan
Kains, Jean-Pierre
Delree, Paul
Keppens, Carine
Sotiriou, Christos
Piccart, Martine J
Cardoso, Fatima
More authors (13 more) Less
Language :
English
Title :
Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC).
Publication date :
2007
Journal title :
European Journal of Cancer
ISSN :
0959-8049
eISSN :
1879-0852
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
43
Issue :
4
Pages :
725-35
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
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