Her-2/neu-positive tumors account for approximately 20% of all breast cancer and these tumors carry poor prognosis. Trastuzumab and lapatinib are 2 agents that have gained FDA approval for treating Her-2/neu-positive breast cancer. Trastuzumab has been shown to improve all endpoints when added to chemotherapy compared to chemotherapy alone, both in the adjuvant and metastatic phases. The addition of lapatinib to capecitabine has recently been shown to improve time to progression in trastuzumab-refractory patients with unique activity against brain metastasis. In spite of their impressive results, a significant fraction of patients still develop either primary or secondary resistance, a fact that entails the discussion of possible mechanisms of resistance. Biomarkers including PTEN, p95HER2, IGF1R and others have been linked to response to Her-2/neu-targeting agents. In this article, we overview the Her-2/neu signaling pathways and how a better understanding of the different molecular aspects of this oncogene could serve in optimizing the use of Her-2/neu-targeting agents. We also discuss the preclinical and clinical data of these biomarkers that may guide clinicians in choosing the right drug whenever possible.
(c) 2008 S. Karger AG, Basel.