ESR1 and breast cancer: ,55 In BC cases involving ESR1, genes like progesterone receptor (PR), epoxy hydrolase 2, lipocalin 2, and interferon α-inducible protein 27 are silenced due to CpG island methylation.55, 56, 57 Recent research suggests that DNA methylation regulates ER-mediated intercellular adhesion genes, potentially promoting metastatic BC involvement.58