HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.
Br J Cancer
; 108(3): 668-75, 2013 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-23348520
ABSTRACT
BACKGROUND:
In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease.METHODS:
We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab.RESULTS:
Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles 4% of patients had HER2 gene amplification (RHER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months 2.5 vs 3.9 vs 7.6, respectively; median OS in months 4.2 vs 9.7 vs 13, respectively).CONCLUSION:
HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
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Receptor ErbB-2
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Dosagem de Genes
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article