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 151–200 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 I654V1
(predisposing)	Malignant Breast Neoplasm	Predisposing	B	Supports Predisposition	3	submitted	EID7236 The confirmed variants Ile654Val, Ile655Val and Ala1170Pro were analysed in subsequent epidemiological studies on familial breast cancer risk. While Ala1170Pro resides within a C-terminally located re…

Cohorts

Alteration frequency by cohort (177)

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

cbioportalObserved177 cohort rows (showing 27, 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
Prostate Cancer-IDH Driver Mutant Cohort (MSK, 2024) prad_idhmut_msk_2025	Prostate Adenocarcinoma	Ssm	1	99	1%

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 Kinase Domain Mutation2
Afatinib	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID959 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
Trastuzumab	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID1043 This was a retrospective study of patients with advanced HER2-mutant NSCLC who had undergone varied courses of treatment. All tumors were adenocarcinoma with in-frame HER2 exon 20 insertions. In pat… (full text at CIViC) PMID 26598547 · Mazières et al., 2016 · Open in CIViC	civic

ERBB2 L15F2
(oncogenic)	Bladder Urothelial Carcinoma	Oncogenic	D	Does Not Support Oncogenicity	2	submitted	EID11232 Variant found by RNA screening analysis in a UBC (urothelial bladder cancer) cell line (VM-CUBIII). The variant is located in the signal domain. RT112 cells infected with lentiviral vectors containin… (full text at CIViC) PMID 24971884 · de Martino et al., 2014 · Open in CIViC	civic
Lapatinib	Bladder Urothelial Carcinoma	Predictive	D	Does Not Support Sensitivity Response	2	submitted	EID11231 Variant found by RNA screening analysis in a UBC (urothelial bladder cancer) cell line (VM-CUBIII). The variant is located in the signal domain. In regards to the response to lapatinib, after three d… (full text at CIViC) PMID 24971884 · de Martino et al., 2014 · Open in CIViC	civic

ERBB2 L755P3
Lapatinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	2	accepted	EID3005 Cell proliferation analysis of Ba/F3 cells expressing ERBB2-L755P showed IC50 value of 1545nM, and was considered as lapatinib-resistant. PMID 22046346 · Kancha et al., 2011 · Open in CIViC	civic
Osimertinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	1	submitted	EID12107 Osimertinib was effective in achieving a partial response in a patient with stage IV non-small cell lung cancer metastasis in the brain harboring ERBB2 exon 19 c.2262_2264delinsTCC, p.(L755P) variant.… (full text at CIViC) PMID 37197637 · Jonsdottir et al., 2023 · Open in CIViC	civic
Trastuzumab Deruxtecan	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	2	accepted	EID11754 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

ERBB2 L755S11
(prognostic)	HER2 Negative Breast CancerUNRESOLVED	Prognostic	C	Supports Better Outcome	2	submitted	EID8015 Though limited to one case, Ben-Beruch et al provide compelling evidence individuals with HER2 mutations regardless of HER2 IHC status may benefit from neratinib alone or in combination. Case study of… (full text at CIViC) PMID 26358790 · Ben-Baruch et al., 2015 · Open in CIViC	civic
(oncogenic)	Pancreatic Ductal Adenocarcinoma	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11557 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
Canertinib	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	submitted	EID10022 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
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID4519 In an in vitro study, NCI-H508 cell lines expressing an ERBB2 L755S mutation demonstrated resistance to cetuximab treatment (IC50 > 200 ug/mL) compared with NCI-H508 cells expressing ERBB2 wild type (… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC	civic
Lapatinib	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	5	accepted	EID241 The L755S mutation was shown to confer resistance to lapatinib in MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2. PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	2	accepted	EID3004 Cell proliferation analysis of Ba/F3 cells expressing ERBB2-L755S showed IC50 value of >2000nM, and was considered as lapatinib-resistant. PMID 22046346 · Kancha et al., 2011 · Open in CIViC	civic
Neratinib	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	5	accepted	EID283 The L755S mutation showed mild response to neratinib in MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2. PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
Capecitabine + NeratinibCombination	Triple-Negative Breast CarcinomaALIAS	Predictive	C	Supports Sensitivity Response	2	submitted	EID8055 This patient originally presented in the clinic with an ER+, PR-, and HER2- mass on the left breast and bone metastasis. Family history showed negative germline mutations in BRCA1/2. Patient responded… (full text at CIViC) PMID 26358790 · Ben-Baruch et al., 2015 · Open in CIViC	civic
Trastuzumab Deruxtecan	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	2	submitted	EID12233 In the phase 2 DESTINY-Lung02 trial, 152 metastatic NSCLC patients harbouring mutations in ERBB2 (HER2) were treated with the HER2 antibody-drug-conjugate (ADC) trastuzumab deruxtecan (5.4 mg/kg or 6.… (full text at CIViC) PMID 37694347 · Goto et al., 2023 · Open in CIViC	civic
Fluorouracil + Leucovorin + TrastuzumabCombination	Colorectal Adenocarcinoma	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID4955 Patient was a 35 year old male who was treated with pseudoadjuvant FOLFOX chemotherapy. Patient relapsed and was found to have an ERBB2 L755S kinase domain mutation along with mutations in APC and BRA… (full text at CIViC) PMID 27626067 · Aung et al., 2016 · Open in CIViC	civic
Lapatinib + Neratinib + TrastuzumabCombination	Malignant Colon Neoplasm	Predictive	D	Supports Sensitivity Response	4	accepted	EID1176 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

ERBB2 L755_T759del3
(functional)	—UNRESOLVED	Functional	D	Supports Neomorphic	3	submitted	EID10026 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
Lapatinib	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	3	submitted	EID10021 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
Neratinib	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	2	accepted	EID281 In MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2, cells expressing the in-frame deletion of amino acids 755-759 were shown to be sensitive to neratinib. PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic