ESR1 and neoplasm: These mechanisms include, for example, acquired mutations of the ESR1 gene in response to endocrine loss, the constitutive activation of cyclin-dependent kinases (CDK4-6), the dysregulation in the cross-talk between ERα and growth factor receptor signaling, epigenetic alterations and modifications by histone deacetylase (HDAC), as well as interactions with the tumor microenvironment and host immune response [8].