Future investigations will need to assess the role of ER-β, taking into account an everchanging scenario in which both ER biology and endocrine treatment paradigms for BC are rapidly evolving as highlighted by the discovery of multiple ER-β variants [32] and by the increasing inclusion of aromatase inhibitors, either upfront or in switching/sequencing strategies, in the adjuvant treatment plan of patients with early BC [33]. This evidence concerns the gene ESR2 and breast cancer.