ERBB2 and breast carcinoma: Not surprisingly, retrospective analyses of two phase II trials (TDM4258g and TDM4374g) carried out in advanced breast cancer revealed that patients with HER2-positive cancer (defined either as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization +) had more frequent responses to T-DM1 than patients who had HER2-normal cancer; in TDM4258g the objective response rates were 34% and 5%, respectively, and in TDM4374g, 41% and 20%, respectively [41-43].