Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis

Br J Cancer. 2014 Aug 26;111(5):918-26. doi: 10.1038/bjc.2014.398. Epub 2014 Jul 15.


Background: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.

Methods: We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.

Results: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.

Conclusions: Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Estrogen Receptor beta / metabolism*
  • Female
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis / pathology*
  • Middle Aged
  • Prognosis
  • Young Adult


  • Estrogen Receptor beta