ERBB2 and breast carcinoma: Monoclonal antibodies commonly used in treating HER2+ breast cancers, including trastuzumab, work by binding the extracellular domain of HER2 and impact several aspects of HER2-driven signaling, including disruption of the receptor dimerization dynamics and inhibition of extracellular HER2 proteolytic cleavage, receptor internalization, and degradation.