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

• Published in: British journal of cancer Vol. 111; no. 5; pp. 918 - 926
• Main Authors: Rosin, G, de Boniface, J, Karthik, G M, Frisell, J, Bergh, J, Hartman, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.08.2014; Nature Publishing Group
• Subjects: 692/53/2423; 692/699/67/1347; 692/699/67/322; 692/700/565/1331/238; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Drug Resistance; Epidemiology; Estrogen Receptor beta - metabolism; Female; Gynecology. Andrology. Obstetrics; Humans; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis - pathology; Mammary gland diseases; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Prognosis; Tumors; Young Adult; breast cancer; pathology; oestrogen receptor; biomarkers; oncology; endocrine therapy; Estrogen receptor; Breast disease; Hormone therapy; Estrogen; Biological marker; Malignant lymphadenopathy; Malignant hemopathy; Breast cancer; Malignant tumor; Survival; Ovarian hormone; Lymph node metastasis; Mammary gland diseases; Anatomic pathology; Cancerology; Sex steroid hormone; Cancer; Hormonal receptor
• DOI: 10.1038/bjc.2014.398
• ISSN: 0007-0920; 1532-1827

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, ER β 1, and its splice variant ER β cx is still unclear. Methods: We here report an assessment of ER α , ER β 1 and ER β 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 β 1 and ER β cx were equally distributed among age groups and tumour histological grades. Loss of ER β 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 α and ER β 1. ER β 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 β 1 and ER β cx in breast cancer. Consequently, we suggest that the histopathological assessment of ER β 1 is of value as a prognostic and potentially predictive biomarker.