Dowsett M, Bundred N J, Decensi A, Sainsbury R C, Lu Y, Hills M J, Cohen F J, Veronesi P, O'Brien M E, Scott T, Muchmore D B
Royal Marsden NHS Trust, London, England SM2 5PT.
Cancer Epidemiol Biomarkers Prev. 2001 Sep;10(9):961-6.
Raloxifene is a selective estrogen receptor (ER) modulator approved for prevention and treatment of postmenopausal osteoporosis. This is an exploratory study of raloxifene in primary breast cancer patients.
Postmenopausal women (50-80 years of age), with histological or cytological diagnosis of stage I or II primary breast cancer, were randomly assigned to 14 days of placebo, 60 mg/day raloxifene, or 300 mg twice daily (600 mg/day) of raloxifene. A core biopsy of the primary tumor was obtained before therapy, and a representative sample of the excised tumor was obtained from the operative specimen after treatment. Paired baseline and endpoint biopsies from each patient were analyzed for Ki67, apoptosis, and estrogen and progesterone receptors. Treatment group differences in efficacy measurements were primarily evaluated for baseline-to-endpoint change and percentage change using a one-way ANOVA with treatment as the fixed effect.
Of 167 enrolled patients, 143 had evaluable efficacy data. Most breast cancer cases were invasive (98.6%), stage I (76.6%), and ER-positive (83.2%). In patients with ER-positive tumors, Ki67 increased 7% from baseline on placebo and decreased by 21% on 60 mg/day raloxifene (P = 0.015 versus placebo) and by 14% on 600 mg/day raloxifene (P = 0.064 versus placebo). Raloxifene did not affect apoptosis. ER decreased significantly with 60 mg/day or 600 mg/day raloxifene compared with placebo (P < 0.01 for each comparison). Raloxifene had no statistically significant effects on Ki67 among patients with ER-negative tumors. There were no treatment differences in adverse events.
In this exploratory trial, 60 mg/day raloxifene showed a significant antiproliferative effect in ER-positive breast cancer, demonstrated by the decrease in Ki67, with no effect in ER-negative cancer. This provides support for raloxifene having a breast cancer preventive effect in postmenopausal women.
雷洛昔芬是一种选择性雌激素受体（ER）调节剂，已被批准用于预防和治疗绝经后骨质疏松症。这是一项关于雷洛昔芬在原发性乳腺癌患者中的探索性研究。
年龄在50 - 80岁的绝经后女性，经组织学或细胞学诊断为I期或II期原发性乳腺癌，被随机分配接受14天的安慰剂治疗、60毫克/天的雷洛昔芬治疗或雷洛昔芬300毫克每日两次（600毫克/天）的治疗。在治疗前获取原发性肿瘤的核心活检样本，并在治疗后从手术标本中获取切除肿瘤的代表性样本。对每位患者配对的基线和终点活检样本进行Ki67、细胞凋亡以及雌激素和孕激素受体分析。治疗组在疗效测量方面的差异主要通过以治疗为固定效应的单向方差分析来评估基线至终点的变化和百分比变化。
在167名入组患者中，143名有可评估的疗效数据。大多数乳腺癌病例为浸润性（98.6%）、I期（76.6%）且ER阳性（83.2%）。在ER阳性肿瘤患者中，安慰剂组Ki67从基线增加7%，60毫克/天雷洛昔芬组下降21%（与安慰剂相比P = 0.015），600毫克/天雷洛昔芬组下降14%（与安慰剂相比P = 0.064）。雷洛昔芬不影响细胞凋亡。与安慰剂相比，60毫克/天或600毫克/天雷洛昔芬组的ER显著降低（每次比较P < 0.01）。雷洛昔芬对ER阴性肿瘤患者的Ki67无统计学显著影响。不良事件方面无治疗差异。
在这项探索性试验中，60毫克/天的雷洛昔芬在ER阳性乳腺癌中显示出显著的抗增殖作用，表现为Ki67降低，而对ER阴性癌症无作用。这为雷洛昔芬在绝经后女性中具有预防乳腺癌的作用提供了支持。
