Kubista Ernst, Planellas Gomez Juan V M, Dowsett Mitch, Foidart Jean-Michel, Pohlodek Kamil, Serreyn Rudolphe, Nechushkin Michail, Manikhas Alexey G, Semiglazov Victor F, Hageluken Cornelius C M, Singer Christian F
Division of Special Gynecology, Medical University of Vienna, Vienna, Austria.
Clin Cancer Res. 2007 Jul 15;13(14):4185-90. doi: 10.1158/1078-0432.CCR-06-2700.
Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue).
Postmenopausal women with initially stage I/II, estrogen receptor-positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen.
Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0% in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P=0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P=0.031). The incidence of adverse effects was comparable.
In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation.
替勃龙是一种选择性组织雌激素活性调节剂，已被批准用于治疗绝经后妇女的血管舒缩症状。我们进行了一项探索性、双盲、随机、安慰剂对照的试点试验，以研究2.5毫克替勃龙对绝经后妇女乳腺癌的组织特异性影响，特别是对组织增殖的影响（STEM，替勃龙对乳腺癌组织影响的研究）。
患有I/II期原发性雌激素受体阳性（ER+）乳腺癌的绝经后妇女被随机分配接受14天的安慰剂或2.5毫克/天的替勃龙治疗。在治疗前后获取原发性肿瘤的核心活检样本。对基线和相应的治疗后样本分析Ki-67和凋亡指数。
在102名登记患者中，95名有可评估数据。两个治疗组的基线特征具有可比性。乳腺癌病例主要为浸润性（99%），I期或II期（分别为42%和50%），且ER+（99%）。替勃龙组基线时肿瘤内Ki-67表达中位数为13.0%，安慰剂组为17.8%，替勃龙治疗14天后降至12.0%，而安慰剂组升至19.0%。替勃龙组和安慰剂组从基线开始的这种变化无显著差异（Wilcoxon检验；P = 0.17）。当比较治疗组之间从基线凋亡指数的中位数变化时，观察到治疗组之间存在显著差异（替勃龙组，0.0%；安慰剂组，+0.3%；Wilcoxon检验；P = 0.031）。不良反应发生率相当。
在ER+乳腺肿瘤中，给予2.5毫克/天的替勃龙14天对肿瘤细胞增殖无显著影响。
