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 1–50 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
BRAF V600E + ERBB2 Amplification + SMAD4 LOSS + TP53 V218EERBB2 TP53 BRAF SMAD41
Bevacizumab + Lapatinib +

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
Endometrial Carcinoma (MSK, Molecular Oncology 2024) ucs_msk_2024	Endometrial Carcinoma	Ssm	69

Literature

Linked publications (83)

25 per page, newest first.

pubmedPublishedShowing 76–83 of 83 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.
· Genes Dev · 2012 · PMID 22802530 · validated civic_curation pubmed
PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs.
· Oncogene · 2011 · PMID 21358673 · validated civic_curation pubmed
An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.
· Cancer Discov · 2017 · PMID 28274957 · validated civic_curation pubmed
Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2-Amplified Gastrointestinal Carcinomas.
· Clin Cancer Res · 2015 · PMID 26296355 · validated

ERBB2 A1291
(functional)	Malignant NeoplasmALIAS	Functional	D	Supports Unaltered Function	4	rejected	EID7346 A library of P53 mutant vectors and wt control was packaged to lentivirus and infected into p53-null H1299 cells at a concentration yielding 1 integration per cell. Relative abundance of each transcri… (full text at CIViC) PMID 29979965 · Kotler et al., 2018 · Open in CIViC	civic

ERBB2 A1291

(functional)

Malignant NeoplasmALIAS

Functional

Supports Unaltered Function

rejected

EID7346

A library of P53 mutant vectors and wt control was packaged to lentivirus and infected into p53-null H1299 cells at a concentration yielding 1 integration per cell. Relative abundance of each transcri… (full text at CIViC)

PMID 29979965 · Kotler et al., 2018 · Open in CIViC

ERBB2 A775_G776insYVMA5
(oncogenic)	Malignant Lung Neoplasm	Oncogenic	D	Supports Oncogenicity	4	rejected	EID11488 Cell proliferation analysis of NIH 3T3 cells harboring the A775_G776insYVMA insertion exhibit an increase of colony formation in soft agar compared with a wild-type ERBB2 and cells with ERBB2 D845A ki… (full text at CIViC) PMID 22908275 · Greulich et al., 2012 · Open in CIViC	civic
〃	Lung Carcinoma	Oncogenic	D	Supports Oncogenicity	4	submitted	EID11494 Cell proliferation analysis of NIH 3T3 cells harboring the A775_G776insYVMA insertion exhibit an increase of colony formation in soft agar compared with a wild-type ERBB2 and cells with ERBB2 D845A ki… (full text at CIViC) PMID 22908275 · Greulich et al., 2012 · Open in CIViC	civic
Afatinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	4	submitted	EID7320 In a Phase II trial, patients with NSCLC haboring exon 20 HER2-activating mutation received afatinib. The interim analysis, evaluating the 12-week status of the first nine patients.Five patients (55.6… (full text at CIViC) PMID 30825613 · Dziadziuszko et al., 2019 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	submitted	EID7202 Ten patients with heavily pretreated stage IV NSCLC had a documented A775_G776insYVMA ERBB2 mutation by local testing. Treatment with Afatinib showed median time-to-treatment failure (TTF) of 9.6 mont… (full text at CIViC) PMID 30096481 · Peters et al., 2018 · Open in CIViC	civic
Zongertinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID12564 In the multicohort phase 1b Beamion LUNG-1 trial (NCT04886804) of zongertinib in HER2-mutant NSCLC, three cohorts were evaluated by mutation type and prior therapy. In cohort 1 (n = 75; HER2-TKD mutat… (full text at CIViC) PMID 40293180 · Heymach et al., 2025 · Open in CIViC	civic

ERBB2 Amplification37
(prognostic)	Endometrial Serous Adenocarcinoma	Prognostic	B	Supports Poor Outcome	4	accepted	EID1096 In a study of 27 African American and caucasian patients, endometrial adenocarcinoma samples were assessed for HER2 via IHC staining, and association studies were performed using corresponding patient… (full text at CIViC) PMID 15746676 · Santin et al., 2005 · Open in CIViC	civic
(oncogenic)	Malignant Colorectal NeoplasmCURATED_BROADER	Oncogenic	B	Supports Oncogenicity	4	submitted	EID11485 Altered human epidermal growth factor receptor 2 (HER2) signaling caused by genomic amplification of ERBB2 or mutations is oncogenic and has been observed in multiple cancer types. Based on the study,… (full text at CIViC) PMID 29338072 · Ross et al., 2018 · Open in CIViC	civic
〃	Pancreatic Ductal Adenocarcinoma	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11563 The ERRB2 amplification effect in PDAC was studied through CAPAN1 cells and ERBB2-KO (knockout) CAPAN1 cells that were KO using CRISPR (Figure 4C, Supp Table 4), with a 90% reduction of ERBB2 compared… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic
A66	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1381 Pharmacologic (A66; p110alpha specific inhibitor) or genetic (cre-mediated knockout) ablation of the p110alpha PI3K isoform reduced tumor growth and tumor formation, respectively, in athymic mice tran… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC	civic
Afatinib	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID1012 LUX-Breast 1 is a phase 3 trial (NCT01125566) which enrolled 508 patients with metastatic HER2 positive BC who had progressed after adjuvant or first-line trastuzumab. It was thought that the wider ra… (full text at CIViC) PMID 26822398 · Harbeck et al., 2016 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID961 A phase II study involving adult female patients, >=18 years, with stage IIIB or IV HER2-positive (by IHC and/or in situ fluorescence) metastatic breast cancer. All patients were previously treated wi… (full text at CIViC) PMID 22418700 · Lin et al., 2012 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	rejected	EID1010 With multiple mechanisms of HER reprogramming thought to be behind trastuzumab resistance, including increased expression of ErbB members, afatinib, which broadly and irreversibly targets ErbB recepto… (full text at CIViC) PMID 22418700 · Lin et al., 2012 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID1011 This Phase II trial (LUX-Breast 3 - NCT01441596) compared afatinib, afatinib plus vinorelbine, or investigator's choice of treatment. 121 patients with HER2 overexpressing breast cancer with CNS recu… (full text at CIViC) PMID 26596672 · Cortés et al., 2015 · Open in CIViC	civic
〃	Transitional Cell Carcinoma	Predictive	B	Supports Sensitivity Response	2	submitted	EID7810 In this phase II trial, patients with metastatic platinum-refractory urothelial carcinoma (UC) received afatinib (40 mg/day). Among the 21 tumors, five of six patients (83.3%) with ERBB2 (HER2) and/or… (full text at CIViC) PMID 27044931 · Choudhury et al., 2016 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID7807 Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was… (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC	civic
〃	Malignant Gastric Neoplasm	Predictive	D	Supports Sensitivity Response	3	submitted	EID7808 Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was … (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC	civic
〃	Uterine Corpus Endometrial CarcinomaUNRESOLVED	Predictive	D	Supports Sensitivity Response	2	accepted	EID886 Eight uterine cancer cell lines (four with ERBB2 amplification and four without) were treated with scalar concentrations of afatinib. Primary chemotherapy-resistant USC cell lines harbouring ERBB2 gen… (full text at CIViC) PMID 25268372 · Schwab et al., 2014 · Open in CIViC	civic
〃	Pancreatic Adenocarcinoma	Predictive	D	Supports Sensitivity Response	2	accepted	EID962 Afatinib was growth-inhibitory for three pancreatic cancer cell lines but cytotoxic only toward BxPC3 (KRAS wt) and Capan-2 (KRAS mut) cells, both of which express high levels of EGFR, ERBB2, and ERBB… (full text at CIViC) PMID 26668065 · Huguet et al., 2016 · Open in CIViC	civic
Afatinib + Lapatinib + TrastuzumabSubstitutes	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID887 In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to afatinib (n = 10), lapatinib (n = 8), or t… (full text at CIViC) PMID 25537159 · Rimawi et al., 2015 · Open in CIViC	civic
Afatinib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID1013 Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB family members such as increased signaling through ErbB family heterodimers. The irreversible TKI afati… (full text at CIViC) PMID 25370464 · Ring et al., 2015 · Open in CIViC	civic
AKTi-1/2	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID760 Xenografts established from breast cancer cell lines with ERBB2 amplification and PIK3CA mutation (BT474) or PIK3CA mutation alone (MCF7) were effectively inhibited in-vivo with an AKT1/2-inhibitor (A… (full text at CIViC) PMID 18725974 · She et al., 2008 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	4	accepted	EID1686 A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	4	accepted	EID1687 A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID1993 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 aft… (full text at CIViC) PMID 28223103 · Jeong et al., 2017 · Open in CIViC	civic
Capecitabine + Cetuximab + OxaliplatinCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Does Not Support Resistance	1	accepted	EID895 141 patients were analyzed for ERBB2 (HER2) positivity by FISH and/or IHC. Only 6 (4.3%) were ERBB2 positive. These patients did not show a difference in outcome after capecitabine, oxaliplatin and ch… (full text at CIViC) PMID 24146218 · Sclafani et al., 2013 · Open in CIViC	civic
Cetuximab + PanitumumabSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	2	accepted	EID1688 HER2 amplification (FISH) was assessed in 170 KRAS wt mCRC patients treated with cetuximab or panitumumab. HER2 copy number status was significantly correlated with response rate, PFS and OS. Patients… (full text at CIViC) PMID 23348520 · Martin et al., 2013 · Open in CIViC	civic
Dacomitinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID1891 Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amplification. 4 patients with HER2 amplified NSCLC were enrolled in the trial, no one among them had a… (full text at CIViC) PMID 25899785 · Kris et al., 2015 · Open in CIViC	civic
Erlotinib + GefitinibSubstitutes	Lung Adenocarcinoma	Predictive	C	Supports Resistance	1	accepted	EID1393 155 patients with lung adenocarcinomas underwent rebiopsy and genotyping (EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS, PIK3CA and FISH for MET and HER2) after the development of acquired resistance to E… (full text at CIViC) PMID 23470965 · Yu et al., 2013 · Open in CIViC	civic
Ibrutinib	Malignant Esophageal Neoplasm	Predictive	D	Supports Sensitivity Response	3	submitted	EID6929 This study found the clinical BTK/ERBB2 kinase inhibitor, ibrutinib, downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle a… (full text at CIViC) PMID 28830912 · Chong et al., 2018 · Open in CIViC	civic
Lapatinib	Gastric Adenocarcinoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID1023 TyTAN, a Phase III study in Asian patients, looked at addition of tyrosine kinase inhibitor lapatinib to chemptherapy in advanced HER2 positive gastric cancer. Primary endpoint was Overall Survival (… (full text at CIViC) PMID 24868024 · Satoh et al., 2014 · Open in CIViC	civic
〃	Childhood Ependymoma	Predictive	B	Supports Sensitivity Response	1	accepted	EID9778 From a phase one clinical trial, pediatric patients with refractory CNS malignancies were administered 300-1150 mg/m2 twice daily of ERBB2 and EGFR inhibitor lapatinib. The maximum-tolerated dose was … (full text at CIViC) PMID 20713864 · Fouladi et al., 2010 · Open in CIViC	civic
Capecitabine + LapatinibCombination	Malignant Breast Neoplasm	Predictive	A	Supports Sensitivity Response	4	submitted	EID11247 In a phase III, randomized, open-label trial, 408 women with HER2-positive, locally advanced or metastatic breast cancer that, after treatment with regimens that included an anthracycline, a taxane, a… (full text at CIViC) PMID 17192538 · Geyer et al., 2006 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1132 This Phase III trial took patients with locally advanced or metastatic HER2 (ERBB2) positive breast cancer that had progressed on prior trastuzumab treatment. Patients were given capecitabine (n=161)… (full text at CIViC) PMID 17192538 · Geyer et al., 2006 · Open in CIViC	civic
Lapatinib + LetrozoleCombination	Malignant Breast Neoplasm	Predictive	A	Supports Sensitivity Response	4	submitted	EID11248 In a phase III, randomized, double-blind, controlled trial, 219 post-menopausal women with HER2-positive, histologically confirmed stage IIIB/IIIC or IV estrogen receptor-positive and/or progesterone … (full text at CIViC) PMID 19786658 · Johnston et al., 2009 · Open in CIViC	civic
Lapatinib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1007 In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the efficacy of trastuzumab plus lapatinib in a neoadjuvant setting with untreated stage II or IIIA HER2 po… (full text at CIViC) PMID 22493419 · Guarneri et al., 2012 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1009 This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergistic activity between lapatinib and trastuzumab against HER2 positive breast cancer (BC) cells. In th… (full text at CIViC) PMID 20124187 · Blackwell et al., 2010 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID1439 In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast cancer treated with lapatinib plus trasuzumab had higher rates of pathological complete responses than s… (full text at CIViC) PMID 22257673 · Baselga et al., 2012 · Open in CIViC	civic
〃	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID1006 In-vitro studies using ERBB2 over-expressing breast cancer cell lines BT474 and SKBR3 (with ERBB2 amplification) showed apoptosis under either labatinib or trastuzumab treatment. A marked synergistic… (full text at CIViC) PMID 16091755 · Xia et al., 2005 · Open in CIViC	civic
Margetuximab	Malignant Breast Neoplasm	Predictive	A	Supports Sensitivity Response	5	accepted	EID11249 In this phase III, randomized, open-label trial, 536 patients with HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, with at least one being for metastatic disease. T… (full text at CIViC) PMID 33480963 · Rugo et al., 2021 · Open in CIViC	civic
MTOR Kinase Inhibitor PP242	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	2	accepted	EID1613 In a panel of 31 breast cancer cell lines with varied mutation backgrounds, 10 cell lines harbored HER2 (ERBB2) amplification. Sensitivity to the mTORC1/2 inhibitor PP242 was assessed, and 8/10 HER2 p… (full text at CIViC) PMID 21358673 · Weigelt et al., 2011 · Open in CIViC	civic
Neratinib	HER2-Positive Breast CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID761 Oral neratinib showed objective response rates of 24 and 56% respectively in prior-trastuzumab (n=63) and trastuzumab-naive (n=64) cohorts in a Phase II trial. As for the primary endpoint, the 16-week… (full text at CIViC) PMID 20142587 · Burstein et al., 2010 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID8072 A panel of HER2 positive breast cancer cell lines (n=12) displayed greater sensitivity to Neratinib (HKI-272) compared to triple negative breast cancer cell lines (n=15, p=.0002) and luminal breast ca… (full text at CIViC) PMID 24009064 · Canonici et al., 2013 · Open in CIViC	civic