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Table 1 Evidence supporting the origin of ER-negative breast cancers from ER-positive precursors

From: The origins of oestrogen receptor negative breast cancer

Evidence Details
Epidemiological Increased oestrogen exposure mediated by ER is a risk factor for all breast cancers
  Prophylactic oophorectomy in BRCA1 mutation carriers reduces all breast cancers
  ADH (>90% ER-positive cells) is a strong risk factor for all breast cancers
  The proportion of ER-negative breast cancers increases with time (tumour progression)
Histological/pathological All early premalignant breast lesions are strongly ER positive
  ER-positive precursors associated with ER-negative cancers in same breast/patient
Molecular MAPK activation reversibly transforms ER-positive to ER-negative breast cancers
  Methylation ER promoter reversibly transforms ER-positive to ER-negative breast cancers
  Apocrine metaplasia may reversibly transform ER-positive to ER-negative breast cancers
  1. ADH, atypical ductal hyperplasia; ER, oestrogen receptor; MAPK, mitogen-activated protein kinase.