As we previously noted, loss of estrogen-dependent growth and/or developed resistance to endocrine-based therapies resulting in increased tumor aggressiveness and progression, including metastasis, has been attributed to ESR1 mutations, altered MAPK signaling, MYC or transcription factor activation, and/or activation of key growth factors as well as a number of unknown mechanisms [41,198]. Here, ESR1 is linked to neoplasm.