ERBB2 and breast cancer: For example, the T-DM1 ADCs (Kadcyla®), approved by the FDA in 2013 for treatment of HER2− BC, are composed of anti-HER2 IgG1 trastuzumab linked to DM1 through a nonreducible heterobifunctional thioether linkage containing an N-hydroxysuccinimide ester (SMCC), which was found to be less toxic, more efficacious, and pharmacokinetically stable [56].