Molecular distinctions among ERBB2-overexpressing breast cancers
- SS Jeffrey1
© BioMed Central 2005
Published: 17 June 2005
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.