ERBB2 AMPLIFICATION Detail (hg38) (ERBB2)

Information

Genome

Assembly Position
hg19 chr17:37,856,333-37,884,915 View the variant detail on this assembly version.
hg38 chr17:39,700,080-39,728,662
Summary

MGeND

Clinical significance
Variant entry
GWAS entry
Disease area statistics Show details

ClinVar

Clinical Significance
Review star [No Data.]
Show details
Links
Type Database ID Link
Gene MIM 164870 OMIM
HGNC 3430 HGNC
Ensembl ENSG00000141736 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC
MONDO
Disease area statistics
[No Data.]
MGeND
[No Data.]
ClinVar
[No Data.]
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
breast cancer Trastuzumab,Lapatinib D Predictive Supports Sensitivity/Response Somatic 3 16091755 Detail
Her2-receptor positive breast cancer Lapatinib,Trastuzumab B Predictive Supports Sensitivity/Response Somatic 4 22493419 Detail
Her2-receptor positive breast cancer Lapatinib,Trastuzumab B Predictive Does Not Support Sensitivity/Response Somatic 4 26255196 Detail
Her2-receptor positive breast cancer Lapatinib,Trastuzumab B Predictive Supports Sensitivity/Response Somatic 4 20124187 Detail
Her2-receptor positive breast cancer Afatinib B Predictive Supports Sensitivity/Response Somatic 3 22418700 Detail
Her2-receptor positive breast cancer Afatinib B Predictive Supports Sensitivity/Response Somatic 3 26596672 Detail
Her2-receptor positive breast cancer Afatinib B Predictive Does Not Support Sensitivity/Response Somatic 4 26822398 Detail
Her2-receptor positive breast cancer Trastuzumab,Afatinib B Predictive Supports Sensitivity/Response Somatic 3 25370464 Detail
gastric adenocarcinoma Trastuzumab B Predictive Supports Sensitivity/Response Somatic 4 20728210 Detail
gastric adenocarcinoma Lapatinib B Predictive Supports Sensitivity/Response Somatic 3 24868024 Detail
lung non-small cell carcinoma Trastuzumab B Predictive Does Not Support Sensitivity/Response Somatic 2 14679114 Detail
lung non-small cell carcinoma Trastuzumab B Predictive Does Not Support Sensitivity/Response Somatic 3 14967075 Detail
lung small cell carcinoma Trastuzumab,Irinotecan C Predictive Supports Sensitivity/Response Somatic 4 25601188 Detail
lung non-small cell carcinoma Trastuzumab Emtansine D Predictive Supports Sensitivity/Response Somatic 4 24898067 Detail
Her2-receptor positive breast cancer Docetaxel,Trastuzumab,Pertuzumab B Predictive Supports Sensitivity/Response Somatic 5 25693012 Detail
endometrial serous adenocarcinoma B Prognostic Supports Poor Outcome Somatic 4 15746676 Detail
endometrial serous adenocarcinoma Trastuzumab C Predictive Supports Sensitivity/Response Somatic 4 18555254 Detail
endometrial cancer Trastuzumab B Predictive Does Not Support Sensitivity/Response Somatic 2 19840887 Detail
Her2-receptor positive breast cancer Trastuzumab,Neratinib A Predictive Supports Sensitivity/Response Somatic 4 26874901 Detail
Her2-receptor positive breast cancer Trastuzumab A Predictive Supports Sensitivity/Response Somatic 4 16236737 Detail
Her2-receptor positive breast cancer Capecitabine,Lapatinib B Predictive Supports Sensitivity/Response Somatic 4 17192538 Detail
Her2-receptor positive breast cancer Capecitabine,Trastuzumab B Predictive Supports Sensitivity/Response Somatic 4 19289619 Detail
Her2-receptor positive breast cancer Trastuzumab Emtansine B Predictive Supports Sensitivity/Response Somatic 4 24793816 Detail
Her2-receptor positive breast cancer Trastuzumab Emtansine B Predictive Supports Sensitivity/Response Somatic 4 23020162 Detail
Her2-receptor positive breast cancer Pictilisib D Predictive Supports Sensitivity/Response Somatic 3 22802530 Detail
Her2-receptor positive breast cancer A66 D Predictive Supports Sensitivity/Response Somatic 2 22802530 Detail
Her2-receptor positive breast cancer Tgx 221 D Predictive Does Not Support Sensitivity/Response Somatic 3 22802530 Detail
lung adenocarcinoma Gefitinib,Erlotinib C Predictive Supports Resistance N/A 1 23470965 Detail
Her2-receptor positive breast cancer Trastuzumab Emtansine B Predictive Supports Sensitivity/Response Somatic 3 23382472 Detail
Her2-receptor positive breast cancer Pertuzumab,Docetaxel,Trastuzumab B Predictive Supports Sensitivity/Response Somatic 4 22149875 Detail
Her2-receptor positive breast cancer Trastuzumab,Lapatinib B Predictive Supports Sensitivity/Response Somatic 4 22257673 Detail
Her2-receptor positive breast cancer Pilaralisib,Trastuzumab D Predictive Supports Sensitivity/Response Somatic 4 23204226 Detail
gastric adenocarcinoma Trastuzumab A Predictive Supports Sensitivity/Response N/A 4 20728210 Detail
Her2-receptor positive breast cancer Palbociclib,Trastuzumab D Predictive Supports Sensitivity/Response Somatic 2 19874578 Detail
breast cancer MTOR Kinase Inhibitor PP242 D Predictive Supports Sensitivity/Response Somatic 2 21358673 Detail
colorectal cancer Cetuximab B Predictive Supports Resistance N/A 4 22586653 Detail
colorectal cancer Cetuximab B Predictive Supports Resistance N/A 4 22586653 Detail
colorectal cancer Panitumumab,Cetuximab B Predictive Supports Resistance N/A 2 23348520 Detail
colorectal cancer Trastuzumab,Lapatinib B Predictive Supports Sensitivity/Response N/A 4 27108243 Detail
scrotum Paget's disease Trastuzumab C Predictive Supports Sensitivity/Response Somatic 2 25692060 Detail
Her2-receptor positive breast cancer Trastuzumab Emtansine B Predictive Supports Sensitivity/Response Somatic 4 21172893 Detail
lung non-small cell carcinoma Dacomitinib B Predictive Does Not Support Sensitivity/Response N/A 3 25899785 Detail
colorectal cancer Cetuximab B Predictive Supports Resistance Somatic 3 28223103 Detail
Her2-receptor positive breast cancer Trastuzumab B Predictive Supports Sensitivity/Response Somatic 5 11248153 Detail
Her2-receptor positive breast cancer Trastuzumab B Predictive Supports Sensitivity/Response Somatic 5 15911866 Detail
colorectal cancer Trastuzumab,Pertuzumab B Predictive Supports Sensitivity/Response N/A 4 29320312 Detail
bladder carcinoma Pertuzumab,Trastuzumab B Predictive Supports Sensitivity/Response N/A 3 29320312 Detail
biliary tract cancer Pertuzumab,Trastuzumab B Predictive Supports Sensitivity/Response N/A 2 29320312 Detail
salivary gland carcinoma Pertuzumab,Trastuzumab B Predictive Supports Sensitivity/Response N/A 2 29320312 Detail
pancreatic cancer Pertuzumab,Trastuzumab B Predictive Supports Sensitivity/Response N/A 2 29320312 Detail
uterine cancer Pertuzumab,Trastuzumab B Predictive Does Not Support Sensitivity/Response N/A 2 29320312 Detail
colorectal cancer Pertuzumab,Trastuzumab B Predictive Supports Sensitivity/Response Somatic 3 30857956 Detail
breast cancer AKTi-1/2 D Predictive Supports Sensitivity/Response Somatic 3 18725974 Detail
breast cancer Neratinib B Predictive Supports Sensitivity/Response Somatic 3 20142587 Detail
cholangiocarcinoma Trastuzumab,Pertuzumab C Predictive Supports Sensitivity/Response Somatic 3 31453370 Detail
stomach cancer Trastuzumab Deruxtecan B Predictive Supports Sensitivity/Response Somatic 4 31047804 Detail
uterine corpus endometrial carcinoma Afatinib D Predictive Supports Sensitivity/Response Somatic 2 25268372 Detail
Her2-receptor positive breast cancer Lapatinib,Afatinib,Trastuzumab B Predictive Supports Sensitivity/Response Somatic 2 25537159 Detail
colorectal cancer Cetuximab,Capecitabine,Oxaliplatin B Predictive Does Not Support Resistance N/A 1 24146218 Detail
Her2-receptor positive breast cancer Afatinib B Predictive Supports Sensitivity/Response Somatic 3 22418700 Detail
pancreatic adenocarcinoma Afatinib D Predictive Supports Sensitivity/Response N/A 2 26668065 Detail
DisGeNET
[No Data.]
Annotation

Annotations

DescrptionSourceLinks
In-vitro studies using ERBB2 over-expressing breast cancer cell lines BT474 and SKBR3 (with ERBB2 am... CIViC Evidence Detail
In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the eff... CIViC Evidence Detail
This Phase III trial compared the activity of lapatinib vs. trastuzumab vs. sequential trastuzumab f... CIViC Evidence Detail
This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergist... CIViC Evidence Detail
With multiple mechanisms of HER reprogramming thought to be behind trastuzumab resistance, including... CIViC Evidence Detail
This Phase II trial (LUX-Breast 3 - NCT01441596) compared afatinib, afatinib plus vinorelbine, or in... CIViC Evidence Detail
LUX-Breast 1 is a phase 3 trial (NCT01125566) which enrolled 508 patients with metastatic HER2 posit... CIViC Evidence Detail
Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB fami... CIViC Evidence Detail
ToGA, a Phase III study (NCT01041404) addressed use of trastuzumab in HER2 positive advanced gastric... CIViC Evidence Detail
TyTAN, a Phase III study in Asian patients, looked at addition of tyrosine kinase inhibitor lapatini... CIViC Evidence Detail
In this phase II trial with 2 arms, 103 patients with untreated stage IIIB/IV HER2 positive NSCLC we... CIViC Evidence Detail
In this phase II trial a small group of patients with IHC2+ or IHC3+ HER2 NSCLC, in which primary pl... CIViC Evidence Detail
This report details 2 case studies in relapsed HER2 positive SCLC. In the first case, a 50 pack-yea... CIViC Evidence Detail
Efficacy of trastuzumab in HER2 overexpressing NSCLC remains unclear. In this study using a panel o... CIViC Evidence Detail
CLEOPATRA (NCT00567190) was a Phase III, randomized and double-blind, placebo-controlled study of 80... CIViC Evidence Detail
In a study of 27 African American and caucasian patients, endometrial adenocarcinoma samples were as... CIViC Evidence Detail
HER2 expression in uterine serous papillary carcinoma (USPC) is thought to be associated with poor p... CIViC Evidence Detail
This phase II single arm study assessed trastuzumab monotherapy in HER2 positive endometrial cancers... CIViC Evidence Detail
In this two arm, Phase III study (NCT00878709) of the efficacy of a 12 month course of the TKI nerat... CIViC Evidence Detail
HERA was a Phase III trial assessing application of trastuzumab in an extended adjuvant setting. Pa... CIViC Evidence Detail
This Phase III trial took patients with locally advanced or metastatic HER2 (ERBB2) positive breast ... CIViC Evidence Detail
In this Phase III trial, trastuzumab-based treatment was assessed in women with locally advanced or ... CIViC Evidence Detail
The Phase III trial, TH3RESA (NCT01419197), was performed in patients with advanced HER2 breast canc... CIViC Evidence Detail
The EMILIA study (NCT00829166) was a Phase II trial to assess the efficacy of trastuzumab emtansine ... CIViC Evidence Detail
The HER2/Neu mammary tumor mouse model MMTV-NeuT was employed to demonstrate dependence of HER2 tumo... CIViC Evidence Detail
Pharmacologic (A66; p110alpha specific inhibitor) or genetic (cre-mediated knockout) ablation of the... CIViC Evidence Detail
Treatment of cells obtained from MMTV-NeuT mouse mammary tumors with the p110beta selective inhibito... CIViC Evidence Detail
155 patients with lung adenocarcinomas underwent rebiopsy and genotyping (EGFR, AKT1, BRAF, ERBB2, K... CIViC Evidence Detail
In a randomized phase II study, first line treatment of HER2-positive metastatic breast cancer with ... CIViC Evidence Detail
In a randomized phase 3 trial, HER2 positive metastatic breast cancer patients given first-line trea... CIViC Evidence Detail
In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast canc... CIViC Evidence Detail
In 5 trastuzumab resistant HER2 overexpressing breast cancer cell lines, combination of the pan-PI3K... CIViC Evidence Detail
ToGA, a Phase III study (NCT01041404) addressed use of trastuzumab in HER2 positive (overexpression ... CIViC Evidence Detail
In a panel of 47 breast cancer cell lines, HER2 overexpressing cells were among those more sensitive... CIViC Evidence Detail
In a panel of 31 breast cancer cell lines with varied mutation backgrounds, 10 cell lines harbored H... CIViC Evidence Detail
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was ... CIViC Evidence Detail
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was ... CIViC Evidence Detail
HER2 amplification (FISH) was assessed in 170 KRAS wt mCRC patients treated with cetuximab or panitu... CIViC Evidence Detail
Phase 2 study in 27 patients with HER2 positive (IHC, FISH), KRAS wt metastatic colorectal cancer re... CIViC Evidence Detail
A 71-year old male with metastatic extramammary Paget’s disease of the scrotum overexpressing Her2/n... CIViC Evidence Detail
In the single arm Phase II study (TDM4258g) breast cancer patients who had progressed on previous an... CIViC Evidence Detail
Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amp... CIViC Evidence Detail
We identified 142 patients with metastatic colorectal cancer whose tumors harbored both wild-type ex... CIViC Evidence Detail
A randomized clinical trial of 469 patients with previously untreated, HER2-positive, metastatic bre... CIViC Evidence Detail
A randomized clinical trial of 186 patients with previously untreated, HER2-positive, metastatic bre... CIViC Evidence Detail
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment... CIViC Evidence Detail
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment... CIViC Evidence Detail
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment... CIViC Evidence Detail
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment... CIViC Evidence Detail
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment... CIViC Evidence Detail
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment... CIViC Evidence Detail
In update report of a phase 2 trial, Patients with colorectal cancer with HER2 amplification receive... CIViC Evidence Detail
Xenografts established from breast cancer cell lines with ERBB2 amplification and PIK3CA mutation (B... CIViC Evidence Detail
Oral neratinib showed objective response rates of 24 and 56% respectively in prior-trastuzumab and t... CIViC Evidence Detail
A patient with cholangiocarcinoma harboring with ERBB2 amplification detected by circulating tumor D... CIViC Evidence Detail
In a phase 1 trial, patients with HER2-positive gastric cancer were treated with Trastuzumab Deruxte... CIViC Evidence Detail
Eight uterine cancer cell lines (four with ERBB2 amplification and four without) were treated with s... CIViC Evidence Detail
In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage II... CIViC Evidence Detail
141 patients were analyzed for ERBB2 (HER2) positivity by FISH and/or IHC. Only 6 (4.3%) were ERBB2 ... CIViC Evidence Detail
A phase II study involving adult female patients, >=18 years, with stage IIIB or IV HER2-positive (b... CIViC Evidence Detail
Afatinib was growth-inhibitory for three pancreatic cancer cell lines but cytotoxic only toward BxPC... CIViC Evidence Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
ERBB2
Genome
hg38
Position
chr17:39,700,080-39,728,662
Variant Type
cnv
Variant (CIViC) (CIViC Variant)
AMPLIFICATION
Transcript 1 (CIViC Variant)
ENST00000269571.5
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/306
Summary (CIViC Variant)
Her2 (ERBB2) amplifications are seen in up to 20% of breast cancers and were associated with aggressive disease and poor prognosis when discovered. Trastuzumab first found considerable success, and was approved for treatment, in HER2 positive metastatic breast cancer (MBC) which had progressed under chemotherapy. These metastatic cancers nonetheless progressed under trastuzumab, and other forms of therapy were studied for next line treatments, including tyrosine kinase inhibitors. Lapatinib, a reversible inhibitor of tyrosine kinase activity in ErbB1 and ErbB2, and afatinib, an irreversible inhibitor of all 4 ErbB forms were shown to have activity in trastuzumab-progressed HER2 MBC. Interestingly trastuzumab itself also turned out to remain effective in treatment of trastuzumab-progressed HER2 MBC. The LUX-Breast 1 trial compared a TKI-based treatment (afatinib) to a trastuzumab-based treatment of trastuzumab-progressed HER2 MBC, and the LUX-Breast 3 trial addressed TKI application in the context of HER2 MBC with difficult to treat brain metastases. In neither of these cases was the TKI more effective, making successful future replacement of trastuzumab-based therapy with a TKI in trastuzumab-progressed HER2 MBC seem unlikely. Instead, a potential role for TKIs in this disease context is revealed in preclinical work suggesting synergism between TKI and trastuzumab action, and clinical trials with lapatinib or afatinib combined with trastuzumab indicate that dual HER2 blockade may be an effective therapy. Dual antibody HER2 blockade with pertuzumab instead of TKI in HER2 MBC has also recently shown strong results in the CLEOPATRA trial. HER2 overexpression is targeted in neoadjuvant breast cancer treatment, and has also been successfully targeted in gastric cancer.
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