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Breast Cancer Research

Open Access

Molecular distinctions among ERBB2-overexpressing breast cancers

  • SS Jeffrey1
Breast Cancer Research20057(Suppl 2):S.22

Published: 17 June 2005


Breast CancerEpidermal Growth Factor ReceptorHormone Receptor StatusInvasive Breast CarcinomaHER2 Overexpression

HER2 or c-ERBB2/neu is a member of the epidermal growth factor receptor (EGFR) family and encodes a tyrosine kinase receptor. Overexpression of HER2 protein is generally attributable to gene amplification. HER2 is overexpressed in 20–30% of primary invasive breast carcinomas and in a greater proportion of in situ breast cancers. Invasive breast cancers that overexpress HER2 are generally higher stage, show lymph node positivity, and have higher S-phase. Moreover, they are often associated with poor prognosis, particularly in node-positive patients.

Microarray studies have subdivided breast cancers into several subtypes. HER2-overexpressing ER-negative tumors are generally classified within a single subtype denoted ERBB2-overexpressing. However, ER-positive HER2-overexpressing tumors are usually intermixed with other ER-positive tumors that do not show HER2 overexpression.

Our recent population-based study evaluating HER2 overexpression and hormone receptor status has unexpectedly found that the majority of HER2-overexpressing tumors are hormone receptor-positive and are more common than HER2-overexpressing ER-negative breast cancers. This implies that the ERBB2-overexpressing molecular subtype, which is associated with ER-negative status, only includes a minority of HER2-overexpressing tumors. We therefore studied gene expression patterns of HER2-overexpressing breast cancers and found several tumor subtypes with distinctive molecular signatures. These ERBB2-overexpressing subtypes spanned the range of hormone receptor status and highlighted different biological characteristics. Since the clinical course varies among patients with HER2-positive tumors, as does their response to targeted therapy, differences in global gene expression among HER2-overexpressing tumors could be important in distinguishing patients for the design and delivery of individualized targeted therapies.

Authors’ Affiliations

Stanford University, Stanford, California, USA


© BioMed Central 2005