In this case, the reduction in HER-2 protein expression can not be explained by the elimination of expressing HER-2 clones, the patient having received only one injection of Trastuzumab. Also, it can not be explained by chemotherapy that received patient. It is currently known that chemotherapy would not modify the HER-2 status in metastatic lesions .
Tumor heterogeneity can be evoked. The main targets of any therapy in metastatic breast cancer are the metastases. However, in the great majority of cases, HER-2 status is determined on the primary tumour, and there are few published data regarding the comparison of HER-2 status between the primary and the metastatic sites and between multiple distant metastatic sites from the same patient and all have reported a high level of consistency although not complete -. The discordances can be explained by the fact that in several of these studies, HER-2 status analysis was made by IHC only. Another possible explanation may be sample's collection which could be done many years before the present analysis, and therefore some protein degradation might have occurred.
Tumor HER-2 status is generally assessed as protein overexpression by IHC while HER-2 gene amplification is detected by FISH and recently by CISH (Chromogenic in situ hybridization) . It is known that there is a high level of correlation between FISH and IHC in the evaluation of HER-2 status of breast cancers and thus, it is not recommended to make a FISH analysis when HER-2 status is negative by IHC .
In our case, we raise a hypothesis about technical interference related to the injection of Trastuzumab the day before biopsy involving a reduction in HER-2 IHC expression and thus we recommend, in such cases, to make a study by FISH on the same biopsy which can determine HER-2 status pertinently. This deserves to be elucidated by studies with large series.