ERBB2 and breast cancer: Of interest, it is known that in HER2-low or HER2-negative breast cancer, the efficacy of trastuzumab deruxtecan (T-DXd) is not primarily dependent on the internalization of the drug into tumor cells but rather on the extracellular activity of the protease cathepsin L. This enzyme, which is present in the tumor microenvironment, cleaves the T-DXd linker, facilitating payload release and inducing cytotoxicity [14].