Multifactorial Approach to Predicting Resistance to Anthracyclines
Multifactorial Approach to Predicting Resistance to Anthracyclines
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DOI：
10.1200/jco.2010.31.2231
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发表时间：
2011-04-20
影响因子：
45.3
通讯作者：
Sotiriou, Christos
中科院分区：
文献类型：
--
作者：
Desmedt, Christine;Di Leo, Angelo;Sotiriou, Christos
目的：目前缺乏预测乳腺癌对蒽环类药物反应/耐药的有效生物标志物。新辅助原则试验（TOP）研究，其中雌激素受体（ER）阴性肿瘤患者接受蒽环类药物治疗（表阿霉素）单一疗法，专门设计用于评估拓扑异构酶II-α（TOP 2A）的预测价值，并开发基因表达特征以鉴定那些不能从蒽环类药物中获益的患者。其中139例可用于缓解预测分析。主要终点为病理完全缓解（pCR）。TOP 2A和基因表达谱进行了评估，使用前epiraproscopy活检。从ER阴性样本的EORTC（欧洲组织的研究和治疗癌症）10994/BIG（乳腺国际集团）00-01和MDACC（MD安德森癌症中心）2003-0321新辅助试验的基因表达数据被用于验证purposes.ResultsA pCR获得在14%的可评估的患者在TOP试验。TOP 2A扩增与pCR显著相关（P
PurposeValidated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER) -negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-alpha (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines.Patients and MethodsThe TOP trial included 149 patients, 139 of whom were evaluable for response prediction analyses. The primary end point was pathologic complete response (pCR). TOP2A and gene expression profiles were evaluated using pre-epirubicin biopsies. Gene expression data from ER-negative samples of the EORTC (European Organisation for Research and Treatment of Cancer) 10994/BIG (Breast International Group) 00-01 and MDACC (MD Anderson Cancer Center) 2003-0321 neoadjuvant trials were used for validation purposes.ResultsA pCR was obtained in 14% of the evaluable patients in the TOP trial. TOP2A amplification, but not protein overexpression, was significantly associated with pCR (P