ESR2 and adenoma: Mechanistically, ER‐β is the predominant estrogen receptor isoform in normal colonic epithelium and functions as a tumour supressor; its expression declines early in the adenoma-carcinoma sequence, so restoring or activating ER‐β re‐establishes anti‐proliferative, pro‐apoptotic, and anti‐inflammatory signaling, such as down‐modulation of Wnt/β‐catenin and COX‐2 pathway, thereby counteracting early neoplastic growth.