拓扑异构酶-IIα表达作为晚期乳腺癌患者群体的预测标志物，这些患者被随机给予单药阿霉素或单药多西他赛治疗。

Topoisomerase-II alpha expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

作者信息

Durbecq Virginie, Paesmans Marianne, Cardoso Fatima, Desmedt Christine, Di Leo Angelo, Chan Stephen, Friedrichs Kay, Pinter Tamas, Van Belle Simon, Murray Elizabeth, Bodrogi István, Walpole Euan, Lesperance Bernard, Korec Stefan, Crown John, Simmonds Peter, Perren Thimothy J, Leroy Jean-Yves, Rouas Ghizlane, Sotiriou Christos, Piccart Martine, Larsimont Denis

机构信息

Jules Bordet Institute, 125 Boulevard de Waterloo, 1000 Brussels, Belgium.

出版信息

Mol Cancer Ther. 2004 Oct;3(10):1207-14.

PMID:15486187

Abstract

PURPOSE

The predictive value of topoisomerase-II alpha (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel.

EXPERIMENTAL DESIGN

Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m(2) q3wks) with docetaxel (100 mg/m(2) q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1).

RESULTS

Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03-1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94-1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content >10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87-6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04-0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content >10% (OR, 8.31; 95% confidence interval, 1.86-37.03; P = 0.05).

CONCLUSIONS

(a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial.

摘要

目的

评估拓扑异构酶-IIα（topo-II）在接受阿霉素或多西他赛单药随机治疗的晚期乳腺癌患者中的预测价值。

实验设计

收集参加一项随机III期临床试验的患者的原发性肿瘤样本，该试验比较阿霉素单药（75mg/m²，每3周一次）与多西他赛（100mg/m²，每3周一次），并通过免疫组织化学（克隆KiS1）评估topo-II状态。

结果

在108个样本中评估了topo-II状态，阿霉素组55个（51%），多西他赛组53个（49%）。表达topo-II的细胞增加10%与阿霉素总体反应的统计学显著优势比（OR；95%置信区间）为1.09（1.03 - 1.15；P = 0.002）相关，而多西他赛组为1.002（0.94 - 1.07；P = 0.95）。随着topo-II增加，与阿霉素相比，多西他赛总体反应的有利OR在topo-II肿瘤含量>10%的患者中降低至不显著。在多变量分析中，（a）HER-2状态似乎与化疗总体反应呈正相关（OR，2.34；95%置信区间，0.87 - 6.27；P = 0.09）。（b）阿霉素的总体反应显著低于多西他赛的总体反应（OR，0.17；95%置信区间，0.04 - 0.64；P = 0.009），但对于topo-II肿瘤含量>10%的阿霉素治疗患者有显著的交互项（OR，8.31；95%置信区间，1.86 - 37.03；P = 0.05）。