These environmental cues can alter entire signalling pathways downstream of well‐established oncogenic alterations.109 Many tumours may have activating mutations in the most upstream elements of certain signalling cascades, such as RAS, EGFR and HER2, but phosphorylation of downstream factors such as MAP‐kinases or mTOR may be inhibited by environmental factors;110 therefore, even if specific driver genetic alterations are inhibited, no effect will be observed in cells in which these signalling pathways are inhibited by such factors.109, 111. This evidence concerns the gene ERBB2 and neoplasm.