ABSTRACT

Approximately 20% of breast cancers are characterized by overexpression of human epidermal growth factor receptor 2 (HER-2) protein and associated gene amplification. HER-2 testing is an essential part of pathological assessment in breast cancer patients, as HER-2 provides not only prognostic but also predictive information on the response to targeted therapy. A humanized monoclonal antibody against the extracellular domain of HER-2 protein, trastuzumab, has significantly improved treatment outcomes in patients with HER-2-overexpressing breast cancer. Therefore, distinguishing which patients will benefit from this drug is essential. Immunohistochemistry and fluorescence in situ hybridization are used in many laboratories to determine HER-2 status. Both methods require interpretation of the test by a pathologist. Since the correlation between these two methods is nearly below 80% and these techniques are difficult to standardize across laboratories and are subject to interobserver variability, molecular techniques based on the quantitative evaluation of HER-2 messenger RNA (mRNA) have been proposed. More recently, by using quantitative reverse transcription-polymerase chain reaction (Q-RTPCR), the HER2 mRNA levels have been successfully measured, making this assay a potentially specific, highly sensitive, reliable, and cost-effective way of measuring HER2 status. Q-RT-PCR could become the test of choice to evaluate HER2 status in breast cancer. To achieve this result, however, it will be necessary to validate Q-RT-PCR by a multicenter trial, with the inclusion of several testing laboratories. Accurate HER2 testing is essential for quality patient care. However, no gold standard exists for HER2 testing, and an optimal test for evaluation of HER2 status is still being discussed by pathology.