Laroche-Clary A, Chaire V, Le Morvan V, Neuville A, Bertucci F, Salas S, Sanfilippo R, Pourquier P, Italiano A
1] INSERM U916 and University of Bordeaux, Bordeaux, France [2] Institut Bergonié, Bordeaux, France.
Institut Bergonié, Bordeaux, France.
Br J Cancer. 2015 Feb 17;112(4):688-92. doi: 10.1038/bjc.2014.624. Epub 2015 Jan 20.
This study aimed to determine whether the BRCA1 haplotype was associated with trabectedin efficacy in soft-tissue sarcoma (STS) patients.
We analysed BRCA1 single-nucleotide polymorphisms (SNPs) in tumour specimens from 135 advanced STS patients enrolled in published phase 2 trials or in a compassionate-use programme of trabectedin. Forty-four advanced STS patients treated with doxorubicin and 85 patients with localised STS served as controls. The 6-month nonprogression rate and overall survival (OS) were analysed according to BRCA1 haplotype using log-rank tests.
A favourable BRCA1 haplotype (presence of at least one AAAG allele) was significantly associated with an improved 6-month nonprogression rate. It was the only variable significantly associated with OS. No correlations were found between outcomes for patients with localised or advanced STS treated with doxorubicin.
The BRCA1 haplotype represents a potential DNA repair biomarker that can be used for the prediction of response to trabectedin in STS patients.
本研究旨在确定BRCA1单倍型是否与软组织肉瘤（STS）患者使用曲贝替定的疗效相关。
我们分析了135例晚期STS患者肿瘤标本中的BRCA1单核苷酸多态性（SNP），这些患者参加了已发表的2期试验或曲贝替定的同情用药项目。44例接受多柔比星治疗的晚期STS患者和85例局限性STS患者作为对照。使用对数秩检验根据BRCA1单倍型分析6个月无进展率和总生存期（OS）。
一种有利的BRCA1单倍型（存在至少一个AAAG等位基因）与6个月无进展率的改善显著相关。它是与OS显著相关的唯一变量。在用多柔比星治疗的局限性或晚期STS患者的结局之间未发现相关性。
BRCA1单倍型代表一种潜在的DNA修复生物标志物，可用于预测STS患者对曲贝替定的反应。
Zotero 插件