Given the potential for misdiagnosis of HER2 amplification in the absence of CEP17 highlighted by our recent audit, 10 this may represent a particular research priority. This form of HER2 lacks the trastuzumab binding site, enabling activated signaling in the presence of trastuzumab. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Oncogenic activating PI3K mutations have also been implicated in trastuzumab resistance.
In addition to additive or synergistic anti-tumor properties in combination with chemotherapies, trastuzumab has demonstrated synergistic anti-tumor effects when given in combination with lapatinib. Clinical trial demonstrating that continuing trastuzumab even after cancer progression on trastuzumab has clear benefits. Research Recommendation. Cardiac dysfunction associated with trastuzumab.