Interestingly, in metastatic HER2+ breast cancer, copy number alteration burden, specifically copy number loss has been shown to be increased in rapid non responders versus exceptional responders of trastuzumab treatment37 and in breast cancer patients with HER2+ brain metastases38 suggesting that increasing levels of chromosomal instability is a particularly aggressive feature of non-responsive and treatment resistant tumours. This evidence concerns the gene ERBB2 and neoplasm.