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HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
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HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
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Journal Article
HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
2013
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adenocarcinoma - drug therapy
/ Adult
/ Aged
/ Antibodies, Monoclonal - administration & dosage
/ Antibodies, Monoclonal, Humanized
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Female
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Gene Expression Regulation, Neoplastic
/ Humans
/ In Situ Hybridization, Fluorescence
/ Male
/ Mutation
/ Oncology
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins p21(ras)
/ Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
/ Tumors
