TY - JOUR
T1 - HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
AU - Martin, V.
AU - Landi, L.
AU - Molinari, F.
AU - Fountzilas, G.
AU - Geva, R.
AU - Riva, A.
AU - Saletti, P.
AU - De Dosso, S.
AU - Spitale, A.
AU - Tejpar, S.
AU - Kalogeras, K. T.
AU - Mazzucchelli, L.
AU - Frattini, M.
AU - Cappuzzo, F.
N1 - Funding Information:
This work was supported by: Oncosuisse (to MF), Fondazione Ticinese contro il Cancro (to MF), Italian Association for Cancer Research (to FC) and Associazione Oncologia Traslazionale (to FC). ST is a senior clinical investigator of the Fund for Scientific Research Flanders and has received research grants from the Belgian Federation Against Cancer and from the Belgian National Cancer Plan.
PY - 2013/2/19
Y1 - 2013/2/19
N2 - 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 (R:HER2/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.
AB - 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 (R:HER2/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.
UR - http://www.scopus.com/inward/record.url?scp=84875217382&partnerID=8YFLogxK
U2 - 10.1038/bjc.2013.4
DO - 10.1038/bjc.2013.4
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C2 - 23348520
AN - SCOPUS:84875217382
SN - 0007-0920
VL - 108
SP - 668
EP - 675
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -
