RGD Reference Report - Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. - Rat Genome Database

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Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients.

Authors: Sassen, A  Rochon, J  Wild, P  Hartmann, A  Hofstaedter, F  Schwarz, S  Brockhoff, G 
Citation: Sassen A, etal., Breast Cancer Res. 2008 Jan 8;10(1):R2.
RGD ID: 2289942
Pubmed: PMID:18182100   (View Abstract at PubMed)
PMCID: PMC2374953   (View Article at PubMed Central)
DOI: DOI:10.1186/bcr1843   (Journal Full-text)

ABSTRACT: INTRODUCTION: The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intracellular signal transduction pathways resulting in receptor interaction and cross-activation. The most famous family member is HER2, which is a target in Herceptintrade mark therapy in metastatic status and also in adjuvant therapy of breast cancer in the event of dysregulation as a result of gene amplification and resulting protein overexpression. The HER2-related HER receptors have been shown to interact directly with HER2 receptors and thereby mutually affect their activity and subsequent malignant growth potential. However, the clinical outcome with regard to total HER receptor state remains largely unknown. METHODS: We investigated HER1-HER4, at both the DNA and the protein level, using fluorescence in situ hybridisation (FISH) probes targeted to all four receptor loci and also immunohistochemistry in tissue microarrays derived from 278 breast cancer patients. RESULTS: We retrospectively found HER3 gene amplification with a univariate negative impact on disease-free survival (hazard ratio 2.35, 95% confidence interval 1.08 to 5.11, p = 0.031), whereas HER4 amplification showed a positive trend in overall and disease-free survival. Protein expression revealed no additional information. CONCLUSION: Overall, the simultaneous quantification of HER3 and HER4 receptor genes by means of FISH might enable the rendering of a more precise stratification of breast cancer patients by providing additional prognostic information. The continuation of explorative and prospective studies on all HER receptors will be required for an evaluation of their potential use for specific therapeutic targeting with respect to individualised therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Breast Neoplasms disease_progressionIAGP 2289942; 2289942DNA:amplificationRGD 
Breast Neoplasms disease_progressionISOERBB3 (Homo sapiens)2289942; 2289942DNA:amplificationRGD 
Breast Neoplasms disease_progressionISOERBB4 (Homo sapiens)2289942; 2289942DNA:amplificationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Erbb3  (erb-b2 receptor tyrosine kinase 3)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Mus musculus)
Erbb3  (erb-b2 receptor tyrosine kinase 3)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Homo sapiens)
ERBB3  (erb-b2 receptor tyrosine kinase 3)
ERBB4  (erb-b2 receptor tyrosine kinase 4)


Additional Information