Most recently, Kaplan et al reported a patient with metastatic ER-positive, HER2-nonamplified ILC with an activating HER2 mutation (HER2 p780_y781insGSP) whose tumor became resistant to neratinib as well as capecitabine, but whose subsequent leptomeningeal disease exhibited a dramatic response to tucatinib plus capecitabine with a PFS of 10 months.26 The past, future, and immense potential of treating HER2-mutated BC with TKI alone or in combination with ADCs have also been thoroughly reviewed and discussed in their case report. This evidence concerns the gene ESR1 and breast cancer.