This study addresses the hypothesis that altered expression of oestrogen receptor-beta and/or altered relative expression of coactivators and
corepressors of oestrogen receptors are associated with and may be mechanisms of de novo
tamoxifen resistance in oestrogen receptor positive
breast cancer. All cases were oestrogen receptor +, node negative, primary breast tumours from patients who later had no
disease progression (
tamoxifen sensitive) or whose disease progressed while on
tamoxifen (
tamoxifen resistant). Using an antibody to oestrogen receptor-beta that detects multiple forms of this
protein (total) but not an antibody that detects only full-length oestrogen receptor-beta 1, it was found that high total oestrogen receptor beta
protein expressors were more frequently observed in
tamoxifen sensitive tumours than resistant tumours (Fisher's exact test, P=0.046). However, no significant differences in the relative expression of oestrogen receptor beta2, oestrogen receptor beta5 and full-length oestrogen receptor beta1
RNA in the
tamoxifen sensitive and resistant groups were found. Also, when the relative expression of two known coactivators,
steroid receptor RNA activator and amplified in
breast cancer 1
RNA to the known
corepressor, repressor of oestrogen receptor activity
RNA, was examined, no significant differences between the
tamoxifen sensitive and resistant groups were found. Altogether, there is little evidence for altered coregulators expression in breast tumours that are de novo
tamoxifen resistant. However, our data provide preliminary evidence that the expression of oestrogen receptor beta
protein isoforms may differ in primary tumours of
breast cancer patients who prove to have differential sensitivity to
tamoxifen therapy.