Dowsett M, Dixon J M, Horgan K, Salter J, Hills M, Harvey E
Department of Academic Biochemistry, Royal Marsden Hospital, London, United Kingdom.
Clin Cancer Res. 2000 Jun;6(6):2260-7.
Idoxifene is a novel selective estrogen receptor modulator. It has reduced agonist activity on breast and uterine cells compared with tamoxifen and antiproliferative effects in tamoxifen-resistant breast cancer cells. Previous studies have shown that a short course of treatment with other antiestrogens prior to surgery caused a significant reduction of the growth fraction when measured by immunohistological staining using the mouse monoclonal antibody Ki67. In this study, we assessed the effect of idoxifene on biological markers of cell proliferation (Ki67) and apoptosis (TdT-mediated dUTP-biotin nick end labeling), and estrogen and progesterone receptor (ER/PR) expression was also evaluated. Core-cut biopsies were obtained in 77 postmenopausal patients with primary breast cancer at diagnosis. Patients were randomized to 40 mg/day idoxifene or placebo for 14-21 days prior to obtaining a second biopsy sample at surgical resection. The percentage of Ki67-positive cells fell from a mean 19.7 +/- 2.7% (SE) to 13.4 +/- 3.4% in idoxifene-treated ER-positive tumors (n = 30; P = 0.0043), but there was no significant effect in placebo-treated ER-positive tumors (n = 27). No effect was seen on ER-negative tumors in either group. Idoxifene had no significant effect on apoptotic index but produced a statistically significant fall in idoxifene-treated ER immunohistochemical score and a small increase in PR that did not reach statistical significance (0.05 < P < 0.10). Idoxifene was well tolerated in all patients. Idoxifene has an antiproliferative effect in ER-positive but not ER-negative breast cancers, and no significant effect on apoptosis in the short-term.
艾多昔芬是一种新型选择性雌激素受体调节剂。与他莫昔芬相比，它对乳腺和子宫细胞的激动活性降低，并且对他莫昔芬耐药的乳腺癌细胞具有抗增殖作用。先前的研究表明，术前短期使用其他抗雌激素药物治疗，通过使用小鼠单克隆抗体Ki67进行免疫组织化学染色测量时，生长分数会显著降低。在本研究中，我们评估了艾多昔芬对细胞增殖生物学标志物（Ki67）和细胞凋亡（TdT介导的dUTP生物素缺口末端标记）的影响，并且还评估了雌激素和孕激素受体（ER/PR）的表达。在77例绝经后原发性乳腺癌患者确诊时获取了组织芯针活检样本。在手术切除获取第二个活检样本之前，患者被随机分为接受40mg/天艾多昔芬或安慰剂治疗14 - 21天。在接受艾多昔芬治疗的ER阳性肿瘤中（n = 30；P = 0.0043），Ki67阳性细胞百分比从平均19.7±2.7%（SE）降至13.4±3.4%，但在接受安慰剂治疗的ER阳性肿瘤中（n = 27）没有显著影响。两组对ER阴性肿瘤均无影响。艾多昔芬对凋亡指数没有显著影响，但在接受艾多昔芬治疗的患者中，ER免疫组化评分有统计学意义的下降，PR有小幅升高但未达到统计学意义（0.05 < P < 0.10）。所有患者对艾多昔芬耐受性良好。艾多昔芬对ER阳性而非ER阴性乳腺癌具有抗增殖作用，短期内对细胞凋亡无显著影响。
