It is likely that these features directly impact patient prognosis rather than being simply epi-phenomena; with evidence that intra-tumoral HER2 gene copy number heterogeneity marks poor disease-free survival in breast cancer patients [25], and that high intra-tumoral heterogeneity of HER2 protein expression predicts poor progression-free survival and overall survival in gastric cancer patients [17]. This evidence concerns the gene ERBB2 and breast carcinoma.