Kenny F S, Willsher P C, Gee J M, Nicholson R, Pinder S E, Ellis I O, Robertson J F
Professorial Unit of Surgery, Nottingham City Hospital, UK.
Breast Cancer Res Treat. 2001 Jan;65(2):135-44. doi: 10.1023/a:1006469627067.
Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or duration 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 are associated with the quality and duration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score > 10) receiving primary tamoxifen (n = 51 Stage I-II elderly; n = 29 Stage III) underwent sequential tumour biopsies for immunocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Median follow-up is 45 months. By 6-months on therapy three patients had attained complete response (CR), 27 partial response (PR); 44 static disease (SD) and six progression (PD) by UICC criteria. Greater decrease in ER and bcl-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 significantly associated with better quality of response (CR/PR vs SD/PD). Greater 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 with longer DofR. This study demonstrates that greater down-regulation of ER and the ER-regulated protein bcl-2 on primary tamoxifen are significantly associated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.
乳腺癌治疗前雌激素受体（ER）表达可预测内分泌治疗的反应率，但不能预测反应质量或反应持续时间（DofR）。已知抗雌激素可使ER下调。本研究检验了以下假设：ER下调程度及ER调节标记物bcl-2与他莫昔芬反应的质量和持续时间相关。80例ER阳性乳腺癌患者（H评分>10）接受初始他莫昔芬治疗（51例为Ⅰ-Ⅱ期老年患者；29例为Ⅲ期患者），对肿瘤进行序贯活检，以免疫细胞化学方法评估ER、bcl-2和增殖标记物MIB1。中位随访时间为45个月。治疗6个月时，根据国际抗癌联盟（UICC）标准，3例患者达到完全缓解（CR），27例部分缓解（PR）；44例疾病稳定（SD），6例进展（PD）。从治疗前到6周，ER和bcl-2 H评分的更大降低（p = 0.035，p = 0.037）以及从治疗前到6个月，ER和bcl-2 H评分的更大降低（p = 0.058，p = 0.036）与更好的反应质量（CR/PR vs SD/PD）显著相关。bcl-2 H评分在6周和6个月时的更大降低（p = 0.041，p = 0.036）以及MIB1在6周时的降低（p = 0.013）与更长的DofR显著相关。本研究表明，在初始他莫昔芬治疗时，ER及ER调节蛋白bcl-2的更大下调与ER阳性乳腺癌更好的反应质量显著相关，而bcl-2和增殖标记物MIB1与更长的反应持续时间显著相关。
