However, dissection of these mechanisms of action is complicated by physical and functional interactions between ERα and SIRT1, where: (i) ERα is a SIRT1 substrate (Kim et al., 2006; Ji Yu et al., 2011), and (ii) SIRT1 functions as an ER coregulator required for the oncogenic effects of estrogens in breast cancer (Elangovan et al., 2011). This evidence concerns the gene ESR1 and breast carcinoma.