ERBB2 and breast cancer: HER2-positive breast cancer in the advanced settings prolongs both PFS and OS when combined with chemotherapy and it has become the standard strategy.12,257,258 Despite the remarkable therapeutic impact of anti-HER2 considering the previous outcomes, some HER2-positive patients may initially have primary resistant disease, causing eventual progression, and this pressing the need for other novel therapeutic options.259 We review recent phase III trial data and discuss a practical approach to sequencing of HER2-directed therapy in patients with HER2-positive MBC.