ESR1 and breast cancer: When the METABRIC breast cancer data set was classified into each of the four Gene Expression prognostic Index Using Subtypes (GENIUS) subgroups using a 3-gene classifier (i.e., HER2+, ER-/HER-, ER+/HER2- high proliferation, ER+/HER2- low proliferation) [42, 43], SOX2 expression was found to be significantly higher in the HER2+ and ER+/HER2- high proliferation (luminal B-like) subgroups (Figure 4B, left panel).