[Measurement of HER-2/neu in breast cancer: which methodologic approach?]

HER-2/neu (c-erbB2) is overexpressed or amplified in 15%-35% of breast cancers. HER-2 testing has become of paramount importance as it represents a key therapeutic, prognostic and predictive parameter. HER-2 is associated with ER/PgR negativity, high histologic grade, high proliferative index, and increased number of metastatic lymph nodes. In N+ patients, HER-2 represents a negative prognostic factor. HER-2 also represents a predictive factor. In fact, HER-2+ patients appear to be resistant to the CMF regimen and comparatively more sensitive to anthracyclins such as Herceptin. HER-2 testing is currently performed utilizing two main methods: gene amplification is usually determined by fluorescence in situ hybridization (FISH), whereas protein overexpression is determined by immunohistochemistry (IHC). The comparison between FISH and IHC assays demonstrates a considerably high degree of concordance (around 90%). When dealing with cases scored as 3+ (according to the FDA licensed scoring method), such a concordance approaches 100%. In consideration of greater technical simplicity as well as of cost-effectiveness, IHC represents the ideal screening method for HER-2 testing. FISH analysis remains valid for HER-2 evaluation in those cases in which IHC fails to provide unequivocal data.