Gene

ERBB2

erb-b2 receptor tyrosine kinase 2

Explore in graph →CI-GENE-00044905HGNC:3430 ENSG00000141736 NCBI 2064 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (304)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 251–300 of 304 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
ERBB2 T798I3
Afatinib	Malignant Breast Neoplasm	Predictive	D	Does Not Support Resistance	2	submitted	EID6176 Efficacy of afatinib at reducing phosphorylation of key proteins was evaluated by western blot. NR6 mouse fibroblast cells transduced to co-express ERBB2 L869R and T798I responded to afatinib treatmen…

Cohorts

Alteration frequency by cohort (177)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved177 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Stomach Adenocarcinoma (Pfizer and UHK, Nat Genet 2014) stad_pfizer_uhongkong	Gastric Adenocarcinoma	Ssm

Literature

Linked publications (83)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 83 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial.
· JAMA Oncol · 2021 · PMID 33480963 · validated civic_curation pubmed
Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial.
· J Clin Oncol · 2024 · PMID 37870536 · validated civic_curation pubmed
Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
· Lancet Oncol · 2016 · PMID 26874901 · validated civic_curation pubmed
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
· N Engl J Med · 2005 · PMID 16236737

ERBB2 T798M1
Lapatinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	2	accepted	EID3006 Cell proliferation analysis of Ba/F3 cells expressing ERBB2-T798M showed IC50 value of 1433nM, and was considered as lapatinib-resistant. PMID 22046346 · Kancha et al., 2011 · Open in CIViC	civic

ERBB2 T798M1

Lapatinib

Malignant NeoplasmALIAS

Predictive

Supports Resistance

accepted

EID3006

Cell proliferation analysis of Ba/F3 cells expressing ERBB2-T798M showed IC50 value of 1433nM, and was considered as lapatinib-resistant.

PMID 22046346 · Kancha et al., 2011 · Open in CIViC

ERBB2 V777L15
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12103 The V777L variant is located in the tyrosine kinase domain. In vitro kinase assays were conducted using recombinant expression of the isolated HER2 kinase domain. In this system wild-type (WT) HER2 sh… (full text at CIViC) PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted	EID10023 A series of HER2 (ERBB2) mutations (G309A, D769H, D769Y, V777L, P780ins, V824I, R678Q, R896C, del755-759, and L755S) were functionally characterized and tested for sensitivity to lapatinib or neratini… (full text at CIViC) PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
(oncogenic)	Pancreatic Ductal Adenocarcinoma	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11559 HPNE cells infected with lentiviral vectors containing the variant did show significant phosphorylation of ERBB2 (Supplementary Figure 1) compared to WT (Figure 2A and B). The variant also exhibits an… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted	EID12105 To model HER2 missense mutations found in tumors without HER amplification, a targeted gene knock-in method was used to create isogenic MCF-10A and MCF7 human breast epithelial cell lines with a singl… (full text at CIViC) PMID 26508629 · Zabransky et al., 2015 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	2	submitted	EID12104 Wild-type and V777L mutant HER2 proteins were ectopically expressed in NIH3T3 cells. The variant form of HER2 supported anchorage-independent growth in soft agar while the wild-type form did not and … (full text at CIViC) PMID 25720673 · Bellmunt et al., 2015 · Open in CIViC	civic
Afatinib	Malignant Breast Neoplasm	Predictive	C	Supports Sensitivity Response	1	accepted	EID11690 In this phase II NCI-MATCH trial, a patient with ER+ invasive ductal breast cancer with ERBB2 V777L mutation was treated with afatinib. A RECIST response was reported in the patient, however, it wasn'… (full text at CIViC) PMID 35939768 · Bedard et al., 2022 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID4452 In an in vitro study, NCI-H508 cell lines expressing an ERBB2 V777L mutation demonstrated resistance to cetuximab treatment (IC50 >200 ug/ml) compared to NCI-H508 cells expressing ERBB2 wild-type (IC5… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC	civic
Lapatinib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID9697 Ba/F3 cells expressing ERBB2 V777L were treated with lapatinib and showed an IC50 value of 27nM, compared to 30nM for wild-type ERBB2 cells. The authors considered V777L as lapatinib-sensitive. PMID 22046346 · Kancha et al., 2011 · Open in CIViC	civic
Neratinib	Malignant NeoplasmALIAS	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID12106 In the SUMMIT basket trial (NCT01953926) patients with solid tumors of various histologies harboring mutations of either HER2 or HER3 were enrolled and treated with the pan-HER kinase inhibitor nerati… (full text at CIViC) PMID 29420467 · Hyman et al., 2018 · Open in CIViC	civic
〃	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	5	accepted	EID288 In MCF10A cell lines, the V777L mutation was shown to be sensitive to neratinib. PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
〃	Pancreatic Ductal Adenocarcinoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID11569 Neratinib suppresses anchorage-independent growth in transduced HPNE cells with the variant in a concentration-dependent manner (Figure 6B–C) with complete inhibition at a concentration of 0.5 µM (Fig… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic
Afatinib + Lapatinib + Neratinib + OsimertinibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID12101 Ba/F3 mouse lymphoid cells expressing wild-type or V777L mutant HER2 were treated with afatinib, neratinib, osimertinib or DMSO (vehicle) for 72 hours, at which time viable cells were measured using t… (full text at CIViC) PMID 29967253 · Nagano et al., 2018 · Open in CIViC	civic
Trastuzumab	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	submitted	EID12102 Ba/F3 mouse lymphoid cells expressing wild-type or V777L mutant HER2 were treated with afatinib, neratinib, osimertinib or DMSO (vehicle) for 72 hours, at which time viable cells were measured using t… (full text at CIViC) PMID 29967253 · Nagano et al., 2018 · Open in CIViC	civic
Lapatinib + Neratinib + TrastuzumabCombination	Malignant Colon Neoplasm	Predictive	D	Supports Sensitivity Response	4	accepted	EID1177 Colon cancer patient derived xenografts with HER2 mutations are sensitive to HER2 targeted drugs and the greatest tumor reduction was seen with the combination of a tyrosine kinase inhibitor with tras… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC	civic
Trastuzumab + Trastuzumab EmtansineSubstitutes	HER2-Positive Breast CarcinomaALIAS	Predictive	C	Supports Resistance	3	submitted	EID5817 In a cohort of 205 Her2-receptor amplified breast cancers, 20 experienced recurrence after trastuzumab therapy. Of the 20 recurrent cases, only six patients had metastatic sites, excluding brain metas… (full text at CIViC) PMID 27900589 · Hirotsu et al., 2017 · Open in CIViC	civic

ERBB2 Y772_A775DUP10
Afatinib	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID1045 A 55 year old heavily pretreated patient with equivocal HER2 overexpression (IHC2+ and no amplification in FISH) was found to have the HER2 YMVA kinase domain insertion. Afatinib monotherapy resulted… (full text at CIViC) PMID 26559459 · Li et al., 2015 · Open in CIViC	civic
〃	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1888 A Phase II study for use of Afatinib in non- or light smokers with lung adenocarcinoma. Three patients with metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were ide… (full text at CIViC) PMID 22325357 · De Grève et al., 2012 · Open in CIViC	civic
〃	Lung Adenosquamous CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	4	accepted	EID1047 Human HER2 with YVMA insertion was put under a clara cell specific, rtTA promoter system inducible via doxycycline. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung… (full text at CIViC) PMID 19122144 · Perera et al., 2009 · Open in CIViC	civic
Afatinib + SirolimusCombination	Lung Carcinoma	Predictive	D	Supports Sensitivity Response	4	rejected	EID1046 In mice, human HER2 with YVMA insertion was placed under a doxycycline-inducible, clara cell specific promoter. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung tum… (full text at CIViC) PMID 19122144 · Perera et al., 2009 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID960 In preclinical studies of transgenic mice and xenografts, continuous expression of mutant ERBB2 (M774insAYVM or the equivalent A775insYVMA) was found to be essential for tumor maintenance. Furthermore… (full text at CIViC) PMID 19122144 · Perera et al., 2009 · Open in CIViC	civic
Bosutinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID4428 In an in vitro study, ERBB2 A775_G776insYVMA mutation was associated with increased sensitivity to bosutinib treatment (IC50: 0.023�M vs. 3.7�M), as compared to wild-type ERBB2. Sensitivity was determ… (full text at CIViC) PMID 27491651 · Yu et al., 2016 · Open in CIViC	civic
Dacomitinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID1893 Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amplification (N=30). Thirteen tumors harbored identical 12 base pair exon 20 insertions [A775_G776insY… (full text at CIViC) PMID 25899785 · Kris et al., 2015 · Open in CIViC	civic
〃	Lung Adenocarcinoma	Predictive	C	Does Not Support Sensitivity Response	3	rejected	EID1049 In this phase II study (NCT00818441) of dacomitinib in HER2 amplified or mutant NSCLC tumors, a cohort of 12 cases with the AYVM insertion did not show any partial responses to dacomitinib, in contras… (full text at CIViC) PMID 25899785 · Kris et al., 2015 · Open in CIViC	civic
Trastuzumab Deruxtecan	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID11764 In a phase 2 trial, 152 metastatic NSCLC patients harboring mutations in ERBB2 (HER2) treated with 2 different doses of the HER2 ADC trastuzumab deruxtecan (5.4 mg/kg and 6.4 mg/kg) resulted in clinic… (full text at CIViC) PMID 37694347 · Goto et al., 2023 · Open in CIViC	civic
Trastuzumab Emtansine	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1125 A 51-year old female never smoker with stage IV lung adenocarcinoma carrying a HER2 insertion in exon 20 (p.A775_G776insYVMA) by sequencing archived material, HER2 overexpression by IHC (2+) and HER2 … (full text at CIViC) PMID 25789838 · Weiler et al., 2015 · Open in CIViC	civic