The clinical evaluation of HER‐2 status: which test to use?

Abstract

Accurate determination of the status of the type I receptor tyrosine kinase HER-2 in breast carcinomas provides significant insight into patient prognosis and may also inform selection of chemotherapeutic and hormonal treatments. At present, however, the single most important application of HER-2 testing is in the selection of patients for treatment with targeted therapies such as Herceptin. Although, based on current literature, fluorescence in situ hybridization (FISH) detection of HER-2 gene amplification may provide more accurate information in this context, this method is not yet widely available. Therefore, screening by immunohistochemistry (IHC) for HER-2 protein, backed by rigorous quality controls and FISH testing of equivocal cases with intermediate staining intensity, remains the current practice. In laboratories with highly standardized testing and quality assurance procedures, this protocol appears highly effective. Improvements in fixation procedures, standardization of antibodies, and use of automated image analysis may all increase the precision of IHC testing. However, on the basis of current data, there is a case to be made for the wider implementation of FISH testing to determine HER-2 status in breast cancer.

Role of Cyclooxygenase 2 (COX-2) in Prognosis of Breast Cancer

“…COX-2 expression is itself up-regulated by ER via modulation of Activated Protein -1 (AP-1) activity [11]. In breast cancer the human epidermal growth factor receptor type 2 (HER-2) is overexpressed in 20-30 % of tumours due to amplification of the HER-2/neu gene [12]. HER-2/neu acts via Mitogen-activated protein kinase (MAPK) to stimulate COX-2 expression in colorectal cancer cells [13] and can stimulate COX-2 expression in the same way when transfected into breast cancer cells [11,14].…”

Poor survival outcomes in HER2-positive breast cancer patients with low-grade, node-negative tumours

“…All 3 þ (high-intensity) staining specimens were considered positive. All 2 þ (moderate-intensity) staining specimens underwent FISH analysis and those who showed HER2 amplification were also classified as positive by the methods described earlier (Bartlett et al, 2003).…”

“…All 3 þ (high-intensity) staining specimens were considered positive. All 2 þ (moderate-intensity) staining specimens underwent FISH analysis and those who showed HER2 amplification were also classified as positive by the methods described earlier (Bartlett et al, 2003).Analysis SPSS (v15) was used to plot Kaplan -Meier survival curves using breast cancer-specific death as an outcome endpoint (log-rank testing). Cox regression analysis was carried out to evaluate the independence of HER2 in predicting the outcome in conjunction (2009) …”

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

“…However, major drawbacks of IHC are that the results are not quantitative, the interpretation is significantly influenced by several technical factors and the inter-observer variation is quite large. Although these discrepancies are improved by the use of standardised IHC tests (such as the HercepTest), it is generally recommended that (2 þ ) HER2 immunostaining needs to be further validated by fluorescence in situ hybridisation (FISH) analysis (Ellis et al, 2000;Mass et al, 2000;Birner et al, 2001;Bartlett et al, 2003). Despite efforts to standardise these assays, substantial intra-and interlaboratory variability of the results still exist.…”