Although combined endocrine therapy in addition to anti-HER2 therapy without chemotherapy in strongly ER-positive, HER2-positive patients is logical but unproven [32], our survival results for the HER2-positive subtypes within the Intermediate and High Risk categories suggest an opportunity for just such a randomized clinical trial utilizing traditional clinicopathological factors, tumor markers, and gene expression profiling assays. This evidence concerns the gene ESR1 and neoplasm.