Defining a test for HER-2/neu evaluation in breast cancer in the diagnostic setting

In breast cancer amplification of the HER-2/neu oncogene and over-expressio n of the protein product is associated with poor prognosis, predicts respon se to some chemotherapeutic regimens and is the target for Herceptin treatm ent. To date there are several methods to assess the amplification/overexpr ession of HER-2/neu with each having advantages and disadvantages. We have studied amplification and over-expression of HER-2/neu in 250 consecutive c ases of breast cancer (220 invasive and 30 in situ carcinomas) presenting t o the Department of Pathology at Women's College Campus of Sunnybrook and W omen's College Health Sciences Center. Thirty percent of the invasive carci nomas were node positive. HER-B/neu protein overexpression was assessed by immunohistochemistry (IH) using antibody CB11 and amplification of the gene by differential PCR. The percentage of tumor cells showing CB11 staining w as determined and the most significant cut off point for positivity was gre ater than or equal to 10% moderate or strong complete membranous staining. The gene was considered amplified if the density score of the product was g reater than or equal to2. There was 94% concordance between the two methods (P value .0001). Both methods were positive in 16% of cases and negative i n 78% of cases, Discrepant cases were examined by FISH which confirmed the IH results in 9/11 invasive carcinomas. These results show that there is ex cellent concordance between IH and PCR. However, immunohistochemistry is ea sier to perform and cheaper than PCR and could be used in routine assessmen t of HER-B/neu in breast cancer patients.