Life after Trastuzumab: Neu Strategies for HER2-positive Breast Cancer

The importance of neu in breast cancer provided the rationale and impetus for developing agents that targeted the receptor. Proof of therapeutic principle was subsequently established with trastuzumab. Although not minimal, the improved clinical outcomes with the antibody were somewhat counterbalanced by disease relapses which occurred in advanced and adjuvant therapy settings. What this observation suggests is that while tumor response may be due principally to uncoupling the link between cell surface message reception and nuclear gene expression, disease progression appears to involve a re-programmable cellular mainframe that enables alternative tumor growth and survival pathways to become operational. The goal of this paper is to meld biological and therapeutic concepts that have resulted in further advances in the treatment of neu-amplified breast cancers.