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Atlas / Disease / HER2 positive breast carcinoma

HER2 positive breast carcinoma

disease
On this page

Also known as ERBB2 Overexpressing subtype of breast carcinomaHER2 Overexpressing breast carcinomaHER2 Overexpressing subtype of breast carcinomaHER2 Positive breast cancerHer2-receptor positive breast cancer

Summary

HER2 positive breast carcinoma (MONDO:0006244) is a cancer with 9 cohort genes (1 GWAS associations across 9 studies; 8 CIViC-evidence somatic drivers; 1 ClinVar predisposition record) and 349 clinical trials. The dominant Reactome pathway is PI3K events in ERBB2 signaling (4 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Trastuzumab + Neratinib in Her2-receptor Positive Breast Cancer (CIViC Level A); 88 further subtype–drug associations are mapped below. Top therapeutic interventions include trastuzumab, trastuzumab emtansine, and pertuzumab.

At a glance

  • Classification: Cancer
  • Cohort genes: 9
  • GWAS associations: 1
  • ClinVar variants: 1
  • Clinical trials: 349
  • Precision-medicine evidence (CIViC): 89 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameHER2 positive breast carcinoma
Mondo IDMONDO:0006244
EFOEFO:1000294
DOIDDOID:0060079
NCITC53556
SNOMED CT427685000
UMLSC1960398
MedGen743175
Is cancer (heuristic)yes

Also known as: ERBB2 Overexpressing subtype of breast carcinoma · HER2 Overexpressing breast carcinoma · HER2 Overexpressing subtype of breast carcinoma · HER2 Positive breast cancer · HER2 positive breast carcinoma · Her2-receptor positive breast cancer

Data availability: 1 ClinVar variant · 1 GWAS association (9 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › breast carcinoma › breast carcinoma by gene expression profile › HER2 positive breast carcinoma

Related subtypes (7): progesterone-receptor positive breast cancer, progesterone-receptor negative breast cancer, Her2-receptor negative breast cancer, breast tumor luminal A or B, normal breast-like subtype of breast carcinoma, estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer

Subtypes (1): triple-positive breast carcinoma

Genetics & variants

GWAS landscape

1 GWAS associations across 9 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs66633031e-08LGR6C0.03

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90446474Sun X202416,4990Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants that Confer Risk for Breast Cancer.
GCST90454348Zhang H20206,40091,477Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.
GCST90446469Sun X20245,8590Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants that Confer Risk for Breast Cancer.
GCST90446473Sun X20245,8590Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants that Confer Risk for Breast Cancer.
GCST90551898Hayat M20252620Genome-wide association study identifies common variants associated with breast cancer in South African Black women.
GCST90319681Hsu YC20231940The largest genome-wide association study for breast cancer in Taiwanese Han population.
GCST007419Lacson JCA20171941,310Genome-Wide Testing of Exonic Variants and Breast Cancer Risk in the California Teachers Study.
GCST90029050Morra A202100Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.
GCST90029051Morra A202100Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic1

MAF distribution

BucketVariants
common (>=0.05)1
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs66633031202208798C>T0.05intron_variantLGR61e-08Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVarVariant (HGVS)GeneClassificationReview
418524NM_016292.3(TRAP1):c.2053G>A (p.Asp685Asn)DNASE1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 40 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
ERBB2ActBLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCECCIViC #20
ERBB3ActBLCA,BRCA,CESC,CHOL,COADREAD,NBL,PRAD,STAD,UCEC,UCS,UTUCCIViC #1733
ERBB4LoFBLCA,BRCA,CCRCC,CHOL,COADREAD,ESCA,HCC,MEL,PRAD,STADCIViC #1734
FCGR2ACIViC #1842
FCGR3ACIViC #1844
BIRC5CIViC #355
PIK3CAActACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTCCIViC #37
PTENLoFANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTCCIViC #41

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
ERBB2Orphanet:213726Serous carcinoma of the corpus uteri
ERBB2Orphanet:2800Extramammary Paget disease
ERBB2Orphanet:388Hirschsprung disease
ERBB2Orphanet:99976Adenocarcinoma of the oesophagus and oesophagogastric junction
ERBB3Orphanet:137776Lethal congenital contracture syndrome type 2
ERBB3Orphanet:388Hirschsprung disease
ERBB4Orphanet:178469Autosomal dominant non-syndromic intellectual disability
ERBB4Orphanet:803Amyotrophic lateral sclerosis
FCGR3AOrphanet:437552Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity
PIK3CAOrphanet:140944CLOVES syndrome
PIK3CAOrphanet:144Lynch syndrome
PIK3CAOrphanet:168984CLAPO syndrome
PIK3CAOrphanet:201Cowden syndrome
PIK3CAOrphanet:210159Adult hepatocellular carcinoma
PIK3CAOrphanet:221061Familial cerebral cavernous malformation
PIK3CAOrphanet:2495Meningioma
PIK3CAOrphanet:276280Hemihyperplasia-multiple lipomatosis syndrome
PIK3CAOrphanet:295239Macrodactyly of fingers, unilateral
PIK3CAOrphanet:295243Macrodactyly of toes, unilateral
PIK3CAOrphanet:314662Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CAOrphanet:60040Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CAOrphanet:714737Diffuse capillary malformation with overgrowth
PIK3CAOrphanet:90308Capillary-lymphatic-venous malformation with segmental distribution
PIK3CAOrphanet:99802Hemimegalencephaly
PTENOrphanet:109Bannayan-Riley-Ruvalcaba syndrome
PTENOrphanet:137608Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTENOrphanet:145Hereditary breast and/or ovarian cancer syndrome
PTENOrphanet:201Cowden syndrome
PTENOrphanet:210548Macrocephaly-intellectual disability-autism syndrome
PTENOrphanet:2969Proteus-like syndrome
PTENOrphanet:494547Squamous cell carcinoma of the hypopharynx
PTENOrphanet:494550Squamous cell carcinoma of the larynx
PTENOrphanet:500464Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTENOrphanet:500478Squamous cell carcinoma of the oropharynx
PTENOrphanet:502363Squamous cell carcinoma of the oral cavity
PTENOrphanet:502366Squamous cell carcinoma of the lip
PTENOrphanet:65285Lhermitte-Duclos disease
PTENOrphanet:79076Juvenile polyposis of infancy
DNASE1Orphanet:300345Autosomal systemic lupus erythematosus
DNASE1Orphanet:536Systemic lupus erythematosus

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only8
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
ERBB2HGNC:3430ENSG00000141736P04626Receptor tyrosine-protein kinase erbB-2civic_evidence
ERBB3HGNC:3431ENSG00000065361P21860Receptor tyrosine-protein kinase erbB-3civic_evidence
ERBB4HGNC:3432ENSG00000178568Q15303Receptor tyrosine-protein kinase erbB-4civic_evidence
FCGR2AHGNC:3616ENSG00000143226P12318Low affinity immunoglobulin gamma Fc region receptor II-acivic_evidence
FCGR3AHGNC:3619ENSG00000203747P08637Low affinity immunoglobulin gamma Fc region receptor III-Acivic_evidence
BIRC5HGNC:593ENSG00000089685O15392Baculoviral IAP repeat-containing protein 5civic_evidence
PIK3CAHGNC:8975ENSG00000121879P42336Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformcivic_evidence
PTENHGNC:9588ENSG00000171862P60484Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENcivic_evidence
DNASE1HGNC:2956ENSG00000213918P24855Deoxyribonuclease-1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
ERBB2Receptor tyrosine-protein kinase erbB-2Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
ERBB3Receptor tyrosine-protein kinase erbB-3Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
ERBB4Receptor tyrosine-protein kinase erbB-4Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell prolife…
FCGR2ALow affinity immunoglobulin gamma Fc region receptor II-aBinds to the Fc region of immunoglobulins gamma.
FCGR3ALow affinity immunoglobulin gamma Fc region receptor III-AReceptor for the invariable Fc fragment of immunoglobulin gamma (IgG).
BIRC5Baculoviral IAP repeat-containing protein 5Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis.
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformPhosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PTENPhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENDual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
DNASE1Deoxyribonuclease-1Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs.

Protein-family classification

Druggable: 8 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.89

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Kinase412.3×7e-04
Phosphatase218.6×0.010
Antibody/Immunoglobulin26.5×0.048
Other/Unknown10.2×0.999

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
ERBB2Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB3Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB4Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FCGR2AAntibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
FCGR3AAntibody/ImmunoglobulinyesIg_sub, Ig-like_dom, Ig-like_fold
BIRC5Other/UnknownnoBIR_rpt, Baculoviral_IAP
PIK3CAKinaseyes2.7.1.137PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PTENPhosphataseyes3.1.3.16Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
DNASE1Phosphataseyes3.1.21.1Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS

Expression context

Cohort genes with no expression data: 0.

9 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)9
unknown0

Top tissues across cohort

TissueCohort genes
jejunal mucosa2
endothelial cell2
leukocyte2
monocyte2
calcaneal tendon2
lower esophagus mucosa1
right uterine tube1
sural nerve1
dorsal root ganglion1
trigeminal ganglion1
cranial nerve II1
secondary oocyte1
blood1
granulocyte1
embryo1
ganglionic eminence1
ventricular zone1
adrenal tissue1
tendon1
sperm1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
ERBB2276ubiquitousmarkerlower esophagus mucosa, right uterine tube, sural nerve
ERBB3274broadmarkertrigeminal ganglion, jejunal mucosa, dorsal root ganglion
ERBB4226broadmarkerendothelial cell, secondary oocyte, cranial nerve II
FCGR2A144broadmarkerblood, monocyte, leukocyte
FCGR3A130broadmarkergranulocyte, leukocyte, monocyte
BIRC5194ubiquitousmarkerventricular zone, ganglionic eminence, embryo
PIK3CA284ubiquitousmarkercalcaneal tendon, adrenal tissue, tendon
PTEN256ubiquitousmarkersperm, endothelial cell, calcaneal tendon
DNASE1226ubiquitousmarkerduodenum, jejunal mucosa, small intestine Peyer’s patch

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PTEN11,626
ERBB29,659
PIK3CA5,157
ERBB34,511
ERBB44,325
BIRC54,222
FCGR3A3,492
FCGR2A2,618
DNASE11,051

Intra-cohort edges

ABSources
DNASE1FCGR2Astring_interaction
ERBB2ERBB3biogrid_interaction, intact, string_interaction
ERBB2ERBB4intact, string_interaction
ERBB2PIK3CAstring_interaction
ERBB3ERBB4intact, string_interaction
ERBB3PTENintact
FCGR2AFCGR3Astring_interaction
PIK3CAPTENstring_interaction

Structural data

PDB: 9 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PIK3CAP42336135
ERBB2P0462663
BIRC5O1539236
ERBB3P2186023
FCGR3AP0863715
ERBB4Q1530314
PTENP6048412
FCGR2AP123189
DNASE1P248551

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 143. Enrichment computed across 9 evidence-associated genes (8 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
PI3K events in ERBB2 signaling4335.9×3e-08ERBB2, ERBB3, ERBB4, PIK3CA
Signaling by ERBB2 KD Mutants4211.5×1e-07ERBB2, ERBB3, ERBB4, PIK3CA
ERBB2 Activates PTK6 Signaling3305.9×4e-06ERBB2, ERBB3, ERBB4
ERBB2 Regulates Cell Motility3267.7×4e-06ERBB2, ERBB3, ERBB4
Constitutive Signaling by Aberrant PI3K in Cancer463.4×7e-06ERBB2, ERBB3, ERBB4, PIK3CA
SHC1 events in ERBB2 signaling3178.4×9e-06ERBB2, ERBB3, ERBB4
Signaling by ERBB2 TMD/JMD mutants3178.4×9e-06ERBB2, ERBB3, ERBB4
Role of phospholipids in phagocytosis3171.3×9e-06FCGR2A, FCGR3A, PIK3CA
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling448.4×1e-05ERBB2, ERBB3, ERBB4, PIK3CA
Downregulation of ERBB2 signaling3142.8×1e-05ERBB2, ERBB3, ERBB4
Signaling by ERBB23129.8×2e-05ERBB2, ERBB3, ERBB4
PIP3 activates AKT signaling433.4×4e-05ERBB2, ERBB3, ERBB4, PIK3CA
RAF/MAP kinase cascade430.5×5e-05ERBB2, ERBB3, ERBB4, PIK3CA
GRB7 events in ERBB2 signaling2475.8×7e-05ERBB2, ERBB3
PI3K events in ERBB4 signaling2259.6×2e-04ERBB4, PIK3CA
FCGR activation2219.6×3e-04FCGR2A, FCGR3A
Downregulation of ERBB2:ERBB3 signaling2203.9×3e-04ERBB2, ERBB3
Signaling by ERBB2 ECD mutants2167.9×5e-04ERBB2, PIK3CA
GRB2 events in ERBB2 signaling2158.6×5e-04ERBB2, ERBB4
FCGR3A-mediated IL10 synthesis273.2×0.002FCGR2A, FCGR3A
Signaling by ERBB4268.0×0.002ERBB3, ERBB4
Synthesis of PIPs at the plasma membrane252.9×0.004PIK3CA, PTEN
Regulation of actin dynamics for phagocytic cup formation246.0×0.005FCGR2A, FCGR3A
PTEN Loss of Function in Cancer1713.8×0.008PTEN
Downstream TCR signaling232.1×0.009PIK3CA, PTEN
PLCG1 events in ERBB2 signaling1356.9×0.011ERBB2
Drug-mediated inhibition of ERBB2 signaling1356.9×0.011ERBB2
Resistance of ERBB2 KD mutants to trastuzumab1356.9×0.011ERBB2
Resistance of ERBB2 KD mutants to sapitinib1356.9×0.011ERBB2
Resistance of ERBB2 KD mutants to tesevatinib1356.9×0.011ERBB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
phosphatidylinositol 3-kinase/protein kinase B signal transduction5117.0×6e-08ERBB2, ERBB3, FCGR3A, PIK3CA, PTEN
epidermal growth factor receptor signaling pathway4110.1×3e-06ERBB2, ERBB3, ERBB4, PIK3CA
antibody-dependent cellular cytotoxicity2624.1×2e-04FCGR2A, FCGR3A
ERBB2-ERBB4 signaling pathway2624.1×2e-04ERBB2, ERBB4
heart development435.0×2e-04ERBB2, ERBB3, ERBB4, PTEN
positive regulation of epithelial cell proliferation381.4×2e-04ERBB2, ERBB3, ERBB4
ERBB2-ERBB3 signaling pathway2374.5×4e-04ERBB2, ERBB3
cell surface receptor protein tyrosine kinase signaling pathway357.9×4e-04ERBB2, ERBB3, ERBB4
Schwann cell development2234.1×7e-04ERBB2, ERBB3
neurotransmitter receptor localization to postsynaptic specialization membrane2178.3×0.001ERBB2, ERBB4
neuron differentiation333.4×0.001ERBB2, ERBB3, ERBB4
negative regulation of apoptotic process415.4×0.001ERBB2, ERBB3, ERBB4, BIRC5
positive regulation of MAPK cascade326.9×0.002ERBB2, ERBB3, ERBB4
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction326.1×0.003ERBB3, ERBB4, PIK3CA
peptidyl-tyrosine phosphorylation293.6×0.003ERBB2, ERBB4
cell surface receptor signaling pathway321.4×0.004ERBB2, FCGR2A, FCGR3A
cellular response to epidermal growth factor stimulus270.7×0.004ERBB2, ERBB4
cell migration320.5×0.004ERBB4, PIK3CA, PTEN
response to muscle inactivity11872.4×0.006PIK3CA
response to butyrate11872.4×0.006PIK3CA
myelination255.9×0.006ERBB2, ERBB3
synapse assembly251.3×0.006ERBB4, PTEN
wound healing250.6×0.006ERBB2, ERBB3
central nervous system morphogenesis1936.2×0.008ERBB4
chromosome localization1936.2×0.008BIRC5
positive regulation of cardiac muscle tissue development1936.2×0.008ERBB3
regulation of neutrophil mediated cytotoxicity1936.2×0.008DNASE1
establishment of planar polarity involved in nephron morphogenesis1936.2×0.008ERBB4
negative regulation of synaptic vesicle clustering1936.2×0.008PTEN
cranial nerve development1624.1×0.010ERBB3

Therapeutics

Drugs indicated for this disease

10 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AbemaciclibApproved (phase 4)
CapecitabineApproved (phase 4)
FulvestrantApproved (phase 4)
PaclitaxelApproved (phase 4)
PalbociclibApproved (phase 4)
PertuzumabApproved (phase 4)
TrastuzumabApproved (phase 4)
Trastuzumab DeruxtecanApproved (phase 4)
Trastuzumab EmtansineApproved (phase 4)
TucatinibApproved (phase 4)
LapatinibPhase 3 (in late-stage trials)
NeratinibPhase 3 (in late-stage trials)
NiraparibPhase 3 (in late-stage trials)
VinorelbinePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Rifaximin, Utomilumab.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 3

Druggability breadth: 9 of 9 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
ERBB2CLOTRIMAZOLE
ERBB3MOBOCERTINIB
ERBB4MOBOCERTINIB
BIRC5BENZIODARONE
PIK3CAIDELALISIB
DNASE1GENTIAN VIOLET

Top cohort targets by molecule count

SymbolMoleculesMax phase
ERBB2834
PIK3CA674
ERBB4474
ERBB3234
BIRC524
DNASE114
FCGR2A00
FCGR3A00
PTEN00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CLOTRIMAZOLE4ERBB2
ERLOTINIB HYDROCHLORIDE4ERBB2
PONATINIB4ERBB2
AFATINIB4ERBB2, ERBB3, ERBB4
LAPATINIB DITOSYLATE4ERBB2
SORAFENIB4ERBB2
NERATINIB4ERBB2, ERBB3, ERBB4
IBRUTINIB4ERBB2, ERBB4
AFATINIB DIMALEATE4ERBB2, ERBB4
CABOZANTINIB4ERBB2
DACOMITINIB4ERBB2, ERBB4
DACOMITINIB ANHYDROUS4ERBB2, ERBB4
VANDETANIB4ERBB2, ERBB3, ERBB4
TRIBROMSALAN4ERBB2
BOSUTINIB4ERBB2, ERBB3, ERBB4
BITHIONOL4ERBB2
ASTEMIZOLE4ERBB2
EBASTINE4ERBB2
OSIMERTINIB4ERBB2, ERBB3
BRIGATINIB4ERBB2, ERBB4
ACALABRUTINIB4ERBB2, ERBB4
ZANUBRUTINIB4ERBB2, ERBB4
TUCATINIB4ERBB2
TIRABRUTINIB4ERBB2, ERBB4
PACLITAXEL4ERBB2
LAZERTINIB4ERBB2
HEXACHLOROPHENE4ERBB2
DOXORUBICIN4ERBB2
DASATINIB4ERBB2, ERBB3, ERBB4, PIK3CA
ERLOTINIB4ERBB2, ERBB3, ERBB4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
PIK3CA2,034Binding:2009, ADMET:19, Toxicity:4, Functional:2
ERBB21,221Binding:1136, Functional:79, ADMET:6
ERBB4591Binding:579, ADMET:8, Functional:4
ERBB3169Binding:169
BIRC565Binding:63, Functional:2
PTEN8Binding:8
DNASE14Binding:4
FCGR2A1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
ERBB22.7.10.1receptor protein-tyrosine kinase
ERBB32.7.10.1receptor protein-tyrosine kinase
ERBB42.7.10.1receptor protein-tyrosine kinase
PIK3CA2.7.1.137, 2.7.1.153, 2.7.11.1phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PTEN3.1.3.16, 3.1.3.67protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
DNASE13.1.21.1deoxyribonuclease I

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
ERBB21,221
ERBB3169
ERBB4591
PIK3CA2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

26 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

CompoundMax phaseCohort target (bioactivity)
CLOTRIMAZOLE4ERBB2
ERLOTINIB HYDROCHLORIDE4ERBB2
PONATINIB4ERBB2
LAPATINIB DITOSYLATE4ERBB2
SORAFENIB4ERBB2
IBRUTINIB4ERBB2, ERBB4
AFATINIB DIMALEATE4ERBB2, ERBB4
CABOZANTINIB4ERBB2
DACOMITINIB4ERBB2, ERBB4
DACOMITINIB ANHYDROUS4ERBB2, ERBB4
VANDETANIB4ERBB2, ERBB3, ERBB4
TRIBROMSALAN4ERBB2
BOSUTINIB4ERBB2, ERBB3, ERBB4
BITHIONOL4ERBB2
ASTEMIZOLE4ERBB2
EBASTINE4ERBB2
OSIMERTINIB4ERBB2, ERBB3
BRIGATINIB4ERBB2, ERBB4
ACALABRUTINIB4ERBB2, ERBB4
ZANUBRUTINIB4ERBB2, ERBB4
TIRABRUTINIB4ERBB2, ERBB4
LAZERTINIB4ERBB2
HEXACHLOROPHENE4ERBB2
DOXORUBICIN4ERBB2
DASATINIB4ERBB2, ERBB3, ERBB4, PIK3CA
ERLOTINIB4ERBB2, ERBB3, ERBB4

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)6ERBB2, ERBB3, ERBB4, BIRC5, PIK3CA, DNASE1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug3FCGR2A, FCGR3A, PTEN
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
FCGR2A1—
FCGR3A0—
PTEN8—

Clinical trials & evidence

Clinical trials

Clinical trials: 349.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE2130
Not specified95
PHASE147
PHASE335
PHASE1/PHASE227
PHASE2/PHASE39
PHASE44
EARLY_PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06217185PHASE4RECRUITINGThe Efficacy and Safety of Pyrotinib, Trastuzumab Combined With Taxanes in the Treatment of Trastuzumab-treated HER2+ Advanced Breast Cancer (ABC).
NCT06868017PHASE4NOT_YET_RECRUITINGRandomized Controlled Clinical Study of Efficacy and Safety of Initumab Combined with Pyrrotinib and Chemotherapeutic Agents in Neoadjuvant Therapy for HER2-positive Breast Cancer with Different Treatment Cycles
NCT07589699PHASE4NOT_YET_RECRUITINGTrastuzumab Rezetecan (T-DXh) in HER2+ Breast Cancer With Non-pCR After TCbHP
NCT05036005PHASE4UNKNOWNNeoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT01785420PHASE3RECRUITINGPre Operative Trastuzumab in Operable Breast Cancer
NCT03975647PHASE3ACTIVE_NOT_RECRUITINGA Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
NCT04457596PHASE3ACTIVE_NOT_RECRUITINGT-DM1 and Tucatinib Compared With T-DM1 Alone in Preventing Relapses in People With High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial
NCT05132582PHASE3ACTIVE_NOT_RECRUITINGA Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer
NCT05346224PHASE3ACTIVE_NOT_RECRUITINGA Study to Evaluate the Efficacy and Safety of HLX11 vs. EU-Perjeta® in the Neoadjuvant Therapy of HER2-Positive and HR-Negative Early-stage or Locally Advanced Breast Cancer
NCT05388500PHASE3NOT_YET_RECRUITINGProtocol for Herceptin as Adjuvant Therapy With Reduced Exposure to Chemotherapy (PHARE-C)
NCT05426486PHASE2/PHASE3ACTIVE_NOT_RECRUITINGA Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients
NCT05698186PHASE3NOT_YET_RECRUITINGThero2-01S22 in HER2-positive Breast Cancer
NCT05705401PHASE3ACTIVE_NOT_RECRUITINGTesting Radiation and HER2-targeted Therapy Versus HER2-targeted Therapy Alone for Low-risk HER2-positive Breast Cancer
NCT05760612PHASE3RECRUITINGAdjuvant Trastuzumab Plus Neratinib in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer After Neoadjuvant Trastuzumab Plus Pertuzumab
NCT06265428PHASE3ACTIVE_NOT_RECRUITINGA Study to Compare DB-1303/BNT323 Versus T-DM1 in Breast Cancer
NCT06313086PHASE3RECRUITINGDP303c Versus Trastuzumab Emtansine in in Patients With HER2-positive Advanced Breast Cancer
NCT06316531PHASE3ACTIVE_NOT_RECRUITINGA Study Comparing BL-M07D1 With T-DM1 in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer
NCT06830889PHASE3RECRUITINGA Study of BL-M07D1 Versus T-DM1 in the Adjuvant Treatment of HER2-positive Breast Cancer With Residual Invasive Cancer After Neoadjuvant Therapy
NCT06891833PHASE2/PHASE3RECRUITINGA Study of BL-M07D1 With or Without Pertuzumab Versus Taxane + Trastuzumab and Pertuzumab in Neoadjuvant Therapy for HER2-Positive Breast Cancer
NCT06958627PHASE2/PHASE3RECRUITINGThe Impact of Intelligent Patient Management Model on Medication Adherence of Pyrotinib Compared to Traditional Patient Management Model: a Prospective, Multicenter, Randomized Controlled Clinical Study
NCT06968585PHASE3ACTIVE_NOT_RECRUITINGA Study of A166 Versus Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Unresectable or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane Therapy
NCT06992882PHASE3RECRUITINGA Randomized, Open-label, Multi-center Phase III Study Comparing the Efficacy of Oral Chemotherapy Combined With Trastuzumab Versus Paclitaxel Combined With Trastuzumab in the Adjuvant Treatment of HER2-positive, Lymph Node-negative Early Breast Cancer Patients(ORCHID-PLUS)
NCT07043725PHASE3RECRUITINGA Clinical Study of Neoadjuvant Treatment With TQB2102 for Injection for Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer
NCT07366840PHASE2/PHASE3NOT_YET_RECRUITINGRC48 Combined With Chemotherapy in HER2-Positive Advanced Breast Cancer Patients With Prior TOP1i-ADC Failure
NCT07377643PHASE3RECRUITINGIBI354 With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer
NCT07413939PHASE2/PHASE3RECRUITINGRO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
NCT07518173PHASE3NOT_YET_RECRUITINGA Study of BL-M07D1 Combined With Pertuzumab Versus Docetaxel Plus Trastuzumab and Pertuzumab in Patients With First-line HER2-positive Recurrent or Metastatic Breast Cancer
NCT00003440PHASE3COMPLETEDPaclitaxel With or Without Trastuzumab in Treating Patients With or Without HER-2/Neu Breast Cancer That is Inoperable, Recurrent, or Metastatic
NCT00005970PHASE3COMPLETEDDoxorubicin Hydrochloride, Cyclophosphamide, and Pacltaxel With or Without Trastuzumab in Treating Women With HER2-Positive Node-Positive or High-Risk Node-Negative Breast Cancer
NCT00390455PHASE3COMPLETEDFulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive
NCT02003209PHASE3COMPLETEDDocetaxel, Carboplatin, Trastuzumab, and Pertuzumab With or Without Estrogen Deprivation in Treating Patients With Hormone Receptor-Positive, HER2-Positive Operable or Locally Advanced Breast Cancer
NCT02125344PHASE3COMPLETEDA Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)
NCT02213744PHASE2/PHASE3TERMINATEDMM-302 Plus Trastuzumab vs. Chemotherapy of Physician’s Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients
NCT03013504PHASE3COMPLETEDA Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients
NCT03085368PHASE2/PHASE3UNKNOWNA Randomized Controlled Trial of HER-2 Positive Breast Cancer Patients Treated With Lapatinib vs Herceptin
NCT03500380PHASE2/PHASE3UNKNOWNA Study of RC48-ADC Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer With or Without Liver Metastases
NCT03556358PHASE3COMPLETEDTrial to Compare the Safety, Efficacy and Immunogenicity of TX05 With Herceptin® in HER2+ Early Breast Cancer
NCT03588091PHASE3COMPLETEDNeoadjuvant Study of Pyrotinib in Combination With Trastuzumab in Patients With HER2 Positive Breast Cancer
NCT03811418PHASE3WITHDRAWNA Study to Compare Pertuzumab + Trastuzumab + Vinorelbine vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer
NCT04109391PHASE3COMPLETEDExtension Study to Provide Adjuvant Treatment Following Neoadjuvant Treatment and Surgical Resection in Protocol TX05-03

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
TRASTUZUMAB4113
TRASTUZUMAB EMTANSINE421
PERTUZUMAB417
LAPATINIB415
TUCATINIB415
NERATINIB412
TRASTUZUMAB DERUXTECAN410
LOPERAMIDE49
VINORELBINE44
COPANLISIB43
EPIRUBICIN43
GOSERELIN43
MARGETUXIMAB43
ZANIDATAMAB43
ABEMACICLIB42
ERIBULIN42
FULVESTRANT42
IXABEPILONE42
NIRAPARIB42
PACLITAXEL42
AFATINIB41
ALDESLEUKIN41
ATROPINE41
CAPECITABINE41
CARVEDILOL41
CEMIPLIMAB41
COLESEVELAM41
CROFELEMER41
DENILEUKIN DIFTITOX41
DIPHENOXYLATE41

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 89 predictive associations from 111 curated evidence items; also 1 prognostic.

Molecular subtypeTherapyEffectLevelCIViC
ERBB2 AmplificationTrastuzumab + NeratinibSensitivity/ResponseCIViC AEID1113 +2
ERBB2 AmplificationTrastuzumabSensitivity/ResponseCIViC AEID1122 +2
ERBB2 AmplificationCapecitabine + NeratinibSensitivity/ResponseCIViC AEID8048 +1
ERBB2 AmplificationTrastuzumab EmtansineSensitivity/ResponseCIViC BEID1159 +3
ERBB2 AmplificationTrastuzumab + LapatinibSensitivity/ResponseCIViC BEID1007 +2
ERBB2 AmplificationAfatinibSensitivity/ResponseCIViC BEID1011 +2
ERBB2 AmplificationNeratinibSensitivity/ResponseCIViC BEID761 +2
ERBB2 AmplificationLapatinib + TrastuzumabSensitivity/ResponseCIViC BEID1009
ERBB2 AmplificationTrastuzumab + AfatinibSensitivity/ResponseCIViC BEID1013
ERBB2 AmplificationTrastuzumab + Docetaxel + PertuzumabSensitivity/ResponseCIViC BEID1077
ERBB2 AmplificationCapecitabine + LapatinibSensitivity/ResponseCIViC BEID1132
ERBB2 AmplificationCapecitabine + TrastuzumabSensitivity/ResponseCIViC BEID1133
ERBB2 AmplificationPertuzumab + Trastuzumab + DocetaxelSensitivity/ResponseCIViC BEID1437
ERBB2 AmplificationAfatinib + Lapatinib + TrastuzumabSensitivity/ResponseCIViC BEID887
ERBB2 OverexpressionTrastuzumab EmtansineSensitivity/ResponseCIViC BEID4840
FCGR2A H167RTrastuzumabSensitivity/ResponseCIViC BEID1088
FCGR3A F212VTrastuzumabSensitivity/ResponseCIViC BEID1087
PIK3CA MutationEverolimusSensitivity/ResponseCIViC BEID1296
PTEN LossEverolimusSensitivity/ResponseCIViC BEID1297
PTEN LossTrastuzumabResistanceCIViC BEID1385 +4
PIK3CA MutationTrastuzumabResistanceCIViC BEID1384 +1
BIRC5 OverexpressionTrastuzumabResistanceCIViC BEID1449
ERBB3 OverexpressionTrastuzumab EmtansineResistanceCIViC BEID8707
PIK3CA MutationTrastuzumab EmtansineResistanceCIViC BEID8536
PIK3CA MutationCapecitabine + LapatinibResistanceCIViC BEID8705
PTEN LossTrastuzumab EmtansineResistanceCIViC BEID8706
EGFR::ZNF880 FusionPyrotinibSensitivity/ResponseCIViC CEID11215
PIK3CA H1047REverolimus + FulvestrantSensitivity/ResponseCIViC CEID1623
ERBB2 V777LTrastuzumab + Trastuzumab EmtansineResistanceCIViC CEID5817
PTEN ExpressionEverolimus + FulvestrantResistanceCIViC CEID1624

+59 more predictive associations (showing top 30 by evidence level).

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 73

This page pulls from 73 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot