Combined Blockade of Activating <i>ERBB2</i> Mutations and ER Results in Synthetic Lethality of ER+/HER2 Mutant Breast Cancer

<i>ERBB2</i> mutations hyperactivate the HER3/PI3K/AKT/mTOR axis, leading to antiestrogen resistance in ER+ breast cancer. Dual blockade of the HER2 and ER pathways is required for the treatment of ER+/HER2 mutant breast cancers.