Estrogen receptor (ER) β remains is the most important marker of response to hormonal therapy in breast cancer.The role of its sister molecule, ERβ, is much less clear.ERβ exists as 5 functionally distinct isoforms of which ERβ 1is considered the only fully functional isoforms.ERβ1 is constitutively expressed in normal mammary gland but often downregulated in breast cancer.The mechanisms surrounding this are unclear.Over the last few years our lab has examined how ERβ1 is regulated in breast cancer.I will present data describing the genetic and epigenetic mechanisms involved as well as the role of miRNAs in ERβ1 regulation.Our results indicate that ERβ1 expression in breast cancer is subject to complex regulation involving DNA methylation, 5UTRs and miRNAs.