ESR1 and breast cancer: Neratinib is an irreversible HER2 TKI approved for adjuvant treatment of HER2+/estrogen receptor-positive (ER+) early BC following adjuvant-trastuzumab-based therapy, and, in combination with capecitabine, for HER2+ metastatic BC patients who have received two or more prior anti-HER2-based regimens in the metastatic setting.