Recently, we have also demonstrated that a lysine to arginine mutation at residue 303 (K303R) within the hinge domain of ER may potentiate ERα’s role as an effector of leptin intracellular signal transduction, which may enhance cell proliferation, migration and invasiveness, contributing to the more aggressive phenotype of K303R-associated breast cancers (4). Here, ESR1 is linked to breast cancer.