ESR1 and malignant endocrine neoplasm: Disruption of the ER-ERE protein-DNA interactions by XR5944 binding to the duplex major groove is a novel method for inhibiting an ERα-mediated transcriptional response, which represents a potential means to bypass antiestrogen resistance in endocrine cancer therapeutics because ER-DNA binding is required for all antiestrogen-resistant estrogen-independent ERα receptor activations.