Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
Associated Disease
colorectal cancer
Source Database
CIViC Evidence
Description
We identified 142 patients with metastatic colorectal cancer whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF. All patients received cetuximab after oxaliplatin, irinotecan, and fluoropyrimidine failure. HER2 status was determined using immunohistochemistry and silver in situ hybridization and correlated with cetuximab efficacy. Of 142 RAS and BRAF wild-type tumors, we observed 7 cases (4.9%) of HER2 amplification by SISH. After a median follow-up of 13.2 months (range, 1.4-78.1 months), median progression-free survival (PFS) was significantly different according to HER2 status: 3.1 months in patients with HER2 amplification compared with 5.6 months in those with non-amplified HER2 (HR = 2.73; 95% CI = 1.18-6.31; P = 0.019). Overall survival (OS) was not significantly different between groups, although there was a tendency towards shorter OS in patients with HER2-amplified tumors (HR = 0.31; 95% CI = 0.61-2.82; 10.1 vs. 13.5 months; P = 0.488).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1993
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/306
Rating
3
Evidence Type
Predictive
Disease
Colorectal Cancer
Evidence Direction
Supports
Drug
Cetuximab
Evidence Level
B
Clinical Significance
Resistance
Pubmed
28223103
Drugs
Drug NameSensitivitySupported
CetuximabResitance or Non-Reponsetrue