ESR1 and breast cancer: Moreover, with the important recent finding of recurrent LBD hotspot mutations in ESR1 (encoding ERmut) arising during metastatic progression of endocrine-refractory ER-positive breast tumors [14–16], coupled with structural evidence that these ESR1 mutations constitutively activate ERmut in a ligand-independent (and ligand-excluding) manner [17, 18], there is no information yet available about the role, if any, receptor phosphorylation may play when breast cancers become driven by ESR1 mutations like Y537S or D538G.