This paradigm has been totally reversed by the recent development of trastuzumab deruxtecan (DS-8201a or T-DXd) and trastuzumab duocarmazine (SYD985), two novel anti-HER2 agents acting through alternative pharmacological mechanisms including the delivery of targeted cytotoxic agents into cancer cells, with encouraging results obtained in patients with HER2-low tumours [16–19, 26]. This evidence concerns the gene ERBB2 and neoplasm.