ERBB2 and breast cancer: To circumvent these problems, we designed and evaluated for the first time a combination therapeutic strategy that can prevent and/or reverse trastuzumab resistance in vivo. Our data provide, to our knowledge, the first preclinical proof of concept in mice for future clinical trials of combination regimens including trastuzumab and a Notch inhibitor, MRK-003 GSI, for the prevention of tumour recurrence in ErbB-2-positive breast cancer.