ESR1 and breast cancer: Combined blockade of HER2 mutations and ER results in synergistic antitumor activity in vitro and in vivo [88, 89], and the combination of neratinib (a tyrosine kinase inhibitor of HER2, EGFR, HER4, and HER3 heterodimers) and FULV has shown promising activity in metastatic ER+/HER2-mutated BC [91].