In addition, aberrant SIRT1 activity also leads to ER-dependent alterations in FOXO-family transcriptional deregulations (FOXOM1, FOXO3a) especially in triple negative breast cancer (Lee et al., 2016) while SIRT1 overexpression is observed in ER−/Her2+ breast cancer cells with E2 interactions with G-protein coupled ERs (GPER) via activation of EGFR/ERK/c-fos/AP-1 signal transduction pathways (Santolla et al., 2015). The gene discussed is ESR1; the disease is breast cancer.