Whether to determine HER2 status for breast cancer in the primary tumour or in the metastasis.

Trastuzumab has substantially changed the prognosis of breast carcinomas. As HER2 over-expression/amplification is a prerequisite for treatment with trastuzumab, an accurate assessment of HER-2 status is the first step for successful treatment. In metastatic breast cancer, we routinely assess HER2 expression in the primary tumour, assuming that HER2 status remains stable through cancer progression. However, it is frequent to find reports that describe discordance between HER2 expression in primary and metastatic tumours. The aim of this paper was to verify whether HER2 status of breast carcinomas is maintained in the corresponding axillary metastasis. Immunohistochemistry was performed on 52 breast carcinomas and their matched axillary metastasis. HercepTest results were concordant in 46 out of 52 cases (88.5%). FISH proved that the differences observed were clinically relevant in only one of the 52 cases studied (98% concordance). We concluded that HER2 status was stable during axillary metastatic progression. Evaluation of gene HER2 status in axillary metastasis rather than in the primary can be useful in certain situations, e.g., small invasive component intimately mixed with in situ component and difficult to recognize in dark field, no tumor after biopsy, or axillary relapse (in this case we can find occasional de novo amplifications susceptible to trastuzumab treatment).

HER-2 status determination in breast carcinomas. A practical approach.

Accurate evaluation of HER-2 status is crucial in the selection of breast carcinoma patients for trastuzumab (Herceptin) treatment. Various laboratory methods have been used for this purpose. The aim of the present work was to analyse the results obtained in the routine practice by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in determination of HER-2 status. Five hundred and three cases of breast invasive ductal carcinoma were selected to analyse the HER-2 overexpression by immunohistochemistry (HercepTest, Dako). HercepTest 2+ equivocal cases (60) were studied by FISH (PathVysion, Vysis) to determine HER-2 gene amplification. HER-2 overexpression determined by Herceptest was shown in 97/503 cases (19%). FISH performed on equivocal cases demonstrated HER-2 amplification in 11/60 tumours (18%). IHC and FISH together showed HER-2 overexpression/gene amplification in 21% of breast invasive carcinomas. Immunohistochemical determination of HER-2 status represents an easy and standardized method that (in contrast to FISH) can be performed in all pathology laboratories without need of any special microscope and enabling to check the morphologic features of the cells analysed. However, in order to assure the reliability of the results, standardization of fixation protocols, automation of the immunohistochemical procedure, and training of pathologists in the interpretation of the results (scoring criteria) should be a priority. Equivocal HercepTest cases must be analysed by FISH preferably in a reference laboratory.