Just like in the case with CRPC, one of the ligand-independent receptor-positivemechanisms of resistance in breast cancer could the activating mutations of the ER.Mutations of the ESR1 gene, that encodes the ER, have been identified in the LBD of thereceptor in 14–54% of clinical samples from metastatic breast cancer patients andhave also been linked to antihormone resistance (Robinson et al. 2013, Jeselsohn et al. 2014). This evidence concerns the gene ESR1 and breast cancer.