Expression of oestrogen receptor-β in oestrogen receptor-α negative human breast tumours

To analyse the phenotype of breast tumours that express oestrogen receptor-β (ERβ) alone tissue microarrays were used to investigate if ERβ isoforms are associated with specific prognostic markers and gene expression phenotypes in ERα-negative tumours. ERα-negative tumours were positive for ERβ1 in 58% of cases (n=122/210), total ERβ in 60% (n=115/192) and ERβ2/cx in 57% of cases (n=114/199). Oestrogen receptor-β1 and total ERβ were significantly correlated with Ki67 (r=0.28, P<0.0001, n=209; r=0.29, P<0.0001, n=191) and with CK5/6, a marker of the basal phenotype (r=0.20, P=0.0106, n=170; r=0.18, P=0.0223, n=158). ERβ2/cx was strongly associated with p-c-Jun and NF-κBp65 (r=0.53, P<0.0001, n=93; r=0.35, P<0.0001, n=176). This study shows that a range of ERβ isoform expression occurs in ERα-negative breast tumours. While expression of ERβ1, total and ERβ2/cx are correlated, individual forms show associations with certain phenotypes that suggest different roles in subsets of ERα-negative cancers. Based on our in vivo observations, ERβ may have the potential to become a therapeutic target in the specific subcohort of ERα-negative breast cancers.