Change in expression of ER, bcl-2 and MIB1 on primary tamoxifen and relation to response in ER positive breast cancer

Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or durati on of response (DofR). ER is known to be down-regulated by anti-oestrogens. This study has tested the hypothesis that the degree of down-regulation of ER and the ER-regulated marker bcl-2 an associated with the quality and du ration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score greater than or equal to 10) receiving primary tamoxifen (n = 51 Stage I-I I elderly; n = 29 Stage III) underwent sequential tumour biopsies for immun ocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Me dian follow-up is 45 months. By 6-months on therapy three patients had atta ined complete response (CR), 27 partial response (PR); 44 static disease (S D) and six progression (PD) by UICC criteria. Greater decrease in ER and bc l-2 H-score from pre-treatment to 6 weeks (p = 0.035, p = 0.037) and ER and bcl-2 H-score from pre-treatment to 6 months (p = 0.058, p = 0.036) were s ignificantly associated with better quality of response (CR/PR vs SD/PD). G reater 6-week and 6-month reduction in bcl-2 H-score (p = 0.041, p = 0.036) and 6-week reduction in MIB1 (p = 0.013) were significantly correlated wit h longer DofR. This study demonstrates that greater down-regulation of ER a nd the ER-regulated protein bcl-2 on primary tamoxifen are significantly as sociated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.