In contrast, ERβ suppresses the proliferation of tumor cells.4,5 The carcinogenic effect of E2 via ERα has been highlighted by experiments in ER-knockout mice6 and by epidemiological studies on cancer risk in patients who receive female hormone replacement therapy, showing an increased risk to develop breast, gynecologic and endocrine gland cancers. Here, ESR1 is linked to malignant endocrine neoplasm.