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

Background: The expression of oestrogen receptor (ER) alpha characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ER beta 1, and its splice variant ER beta cx is still unclear. Methods: We here report an assessment of ER alpha, ER beta 1 and ER beta cx 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. ER beta 1 and ER beta cx were equally distributed among age groups and tumour histological grades. Loss of ER beta 1 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 ER alpha and ER beta 1. ER beta cx 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 ER beta 1 and ER beta cx in breast cancer. Consequently, we suggest that the histopathological assessment of ER beta 1 is of value as a prognostic and potentially predictive biomarker.