According to a commentary, despite the tangible effect of 1 year of trastuzumab, in the HERA trial the estimated absolute benefit in survival at 12 years is ~7%, and ~30% of patients relapsed within 10 years. It notes that several alternative drugs and schedules of drug administration to improve results in patients with this subtype of breast cancer are being assessed. A simple strategy is to co-administer trastuzumab with chemotherapy, an approach supported by the NCCTG 9831, NSABP B-31 and BCIRG-006 trials. Another rational approach is combination of HER2-targeted therapies based on the promising efficacy of pertuzumab, trastuzumab emtansine, lapatinib tosilate (a small molecule tyrosine-kinase inhibitor of HER2), and neratinib (a potent irreversible oral tyrosine-kinase inhibitor of HER1, HER2, and HER4) in the preoperative and advanced disease settings. It adds that future efforts to optimise therapy for patients with HER2-positive breast cancer will benefit from identification of biomarkers (other than HER2 expression) that match patients and tumours to the most effective therapy.