ESR1 and breast cancer: In ER+ breast cancer cell lines and xenografts resistant to anti-estrogen therapies, treatment with neratinib restored fulvestrant sensitivity in cell lines harboring ERBB2 kinase domain-activating mutations (L755S and V777L), and dual blockade of ER and HER2 with neratinib plus fulvestrant was required to inhibit the growth of these ER+/ERBB2-mutant cell lines23.