Review: significance of, and optimal screening for, HER-2 gene amplification and protein overexpression in breast carcinoma.
Breast carcinoma is a common disease, with an estimated 183,000 new cases expected in the USA during 2000. Whereas early stage patients have high likelihood of cure, only 20-40% of patients with metastatic breast carcinoma respond to presently available chemotherapy. A need exists to identify the underlying biological subsets of morphologically similar carcinomas in order to develop customized therapies for patients who require chemotherapy. The HER-2 receptor tyrosine kinase is overexpressed in 15-30% of breast carcinomas, and is associated with a worse prognosis stage-for-stage. Humanized monoclonal antibody therapy (Herceptin; Genentech Co.) appears to benefit this subset of patients by improving their response rate and survival following anthracycline- or taxane-based chemotherapeutic regimens. Both HER-2 gene amplification and protein overexpression correlate with clinical outcomes, and screening for HER-2 gene amplification appears to be the more informative test. This article reviews data on the HER-2 gene and protein, discusses their association with clinical outcomes, and proposes a strategy for screening for HER-2 excess in formalin-fixed specimens of breast carcinoma.
Funkhouser
W K
WK
Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, 275997525, USA. bill_funkhouser@med.unc.edu
Kaiser-Rogers
K
K
D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
D018719:Erb-b2 Receptor Tyrosine Kinases