ESR1 and cancer: While the lack of ESR1 expression appears to be caused by genetic mutations in only less than 1% of ESR1-negative cancers, there is increasing evidence that epigenetic alterations of cytosine residues at the level of the ESR1 promoter DNA and the posttranslational modification of N-terminal ends of histone proteins are responsible for the absence of ESR1 expression in ESR1-negative cancers [7,8].