The estrogen signaling system is a crucial regulator of metabolic and physiological processes. However, abnormal activation of estrogen signaling may play a role in breast cancer initiation and progression. Crucial to this pathway is the interaction between estrogen receptor alpha (ERα) and various co-transcription activators.1 Although numerous studies have investigated ER coregulators, the protein–protein interaction networks of ERα are not fully understood. Recent research has shown that high chromodomain helicase DNA-binding 4 (CHD4) expression is linked to poor prognosis in various cancers.2,3 In this study, we demonstrated that both CHD4 and ERα contribute to breast cancer progression while providing evidence of the regulatory processes and functional interplay between these two proteins.