ESR1 and breast cancer: Overall, these data support the regulation of HER2 transcription by ligand-dependent ER activity in ER-positive HER2-positive BC cells in which the AKT-mTOR pathway is activated and independent of ER (no or low activation by E2 treatment), compared to cells in which this pathway is activated by ligand-dependent ER activity (ZR75.30) (Figure 5d).