ER-negative breast tumors are resistant to chemotherapeutics targeting ER and estrogen production, and this resistance is partially attributable to ligand-independent activities of ERR1, loss of ER-mediated competition for regulatory cofactors, and the ability of ERR1 to stimulate ER target genes independently of ER, particularly in the breast cancer landscape [6]. The gene discussed is ESR1; the disease is breast carcinoma.