1. ¹Manitoba Institute of Cell Biology, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada, R3E OW3
2. ²Department of Biochemistry and Medical Genetics, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada, R3E OW3
3. ³Department of Pathology, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada, R3E OW3
4. ⁴Department of Surgery, University of Massachusetts Medical School, Worchester. Massachusetts, MA 01655, USA

Correspondence: Dr LC Murphy, Manitoba Institute of Cell Biology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB. R3E OV9, Canada; E-mail: lcmurph@cc.umanitoba.ca

Received 1 July 2002; Revised 4 September 2002; Accepted 19 September 2002.

Abstract

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 2, oestrogen receptor 5 and full-length oestrogen receptor 1 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 protein isoforms may differ in primary tumours of breast cancer patients who prove to have differential sensitivity to tamoxifen therapy.