There has been great progress made in treatment of HER2 positive breast cancer largely due to the results of trastuzumab, however a number of new drugs have been developed that can treat this disease after trastuzumab has failed. The monoclonal antibody pertuzumab and the tyrosine kinase inhibitor lapatinib have very different modes of action but both form effective drug combinations with trastuzumab. This dual HER2 blockade approach has shown promising results both in early trials in the advanced setting and in early neoadjuvant trials. Dr Martine Piccart discusses the design and outcome of these studies and explains how effectively determining which patients will response most to these treatments could help reduce cancer treatment cost and level of adverse effects.