主页 > 医学前沿 >
【medical-news】EORTC 10994/BIG 00-01研究：雌二醇受体
Summary
Background
We have previously described gene-expression signatures that predict growth inhibitory and cytotoxic effects of common chemotherapeutic drugs in vitro. The aim of this study was to confirm the validity of these gene-expression signatures in a large series of patients with oestrogen-receptor-negative breast tumours who were treated in a phase III neoadjuvant clinical trial.
Methods
This trial compares a non-taxane regimen (fluorouracil, epirubicin, and cyclophosphamide [FEC] for six cycles) with a taxane regimen (docetaxel for three cycles followed by epirubicin plus docetaxel [TET] for three cycles) in women with oestrogen-receptor-negative breast cancer. The primary endpoint of the study is the difference in progression-free survival based on TP53 status and will be reported later. Predicting response with gene signatures was a planned secondary endpoint of the trial and is reported here. Pathological complete response, defined as complete disappearance of the tumour with no more than a few scattered tumour cells detected by the pathologist in the resection specimen, was used to assess chemosensitivity. RNA was prepared from sections of frozen biopsies taken at diagnosis and hybridised to Affymetrix X3P microarrays. In-vitro single-agent drug sensitivity signatures were combined to obtain FEC and TET regimen-specific signatures. This study is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00017095.
Findings
Of 212 patients with oestrogen-receptor-negative tumours assessed, 87 patients were excluded. 125 oestrogen-receptor-negative tumours (55 that showed pathological complete responses) were tested: 66 in the FEC group (28 that showed pathological complete responses) and 59 in the TET group (27 that showed pathological complete responses). The regimen-specific signatures significantly predicted pathological complete response in patients treated with the appropriate regimen (p<0·0001). The FEC predictor had a sensitivity of 96% (27 of 28 patients [95% CI 82–99]), specificity of 66% (25 of 38 patients [50–79]), positive predictive value (PPV) of 68% (27 of 40 patients [52–80]), and negative predictive value (NPV) of 96% (25 of 26 patients [81–99]). The TET predictor had a sensitivity of 93% (25 of 27 patients [77–98]), specificity 69% (22 of 32 patients [51–82]), PPV of 71% (25 of 35 patients [55–84]), and NPV of 92% (22 of 24 patients [74–98]). Analysis of tumour size, grade, nodal status, age, and regimen-specific signatures showed that the genomic signatures were the only independent variables predicting pathological complete response at p<0·01. Selection of patients with these signatures would increase the proportion of patients with pathological complete responses from 44% to around 70% in the patients studied here.
Interpretation
We have validated the use of regimen-specific drug sensitivity signatures in the context of a multicentre randomised trial. The high NPV of both signatures may allow early selection of patients with breast cancer who should be considered for trials with new drugs.
http://www.thelancet.com/journals/lanonc/article/PIIS1470204507703455/abstract 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。
fanqingdong2004 wrote:
本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。
Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial
EORTC 10994/BIG 00-01临床试验的亚组研究结果证实可预测乳腺癌新辅助化疗反应的基因标记物
Summary
摘要
Background
背景
We have previously described gene-expression signatures that predict growth inhibitory and cytotoxic effects of common chemotherapeutic drugs in vitro. The aim of this study was to confirm the validity of these gene-expression signatures in a large series of patients with oestrogen-receptor-negative breast tumours who were treated in a phase III neoadjuvant clinical trial.
既往我们已经报道了体外研究中能预测抑制肿瘤细胞生长和常见抗癌药物细胞毒效应的基因标记物。本研究为了证实这些基因在大样本量接受三期新辅助治疗临床试验、雌激素受体阴性乳腺癌患者预测化疗效果的可行性。
Methods
方法
This trial compares a non-taxane regimen (fluorouracil, epirubicin, and cyclophosphamide [FEC] for six cycles) with a taxane regimen (docetaxel for three cycles followed by epirubicin plus docetaxel [TET] for three cycles) in women with oestrogen-receptor-negative breast cancer. The primary endpoint of the study is the difference in progression-free survival based on TP53 status and will be reported later. Predicting response with gene signatures was a planned secondary endpoint of the trial and is reported here. Pathological complete response, defined as complete disappearance of the tumour with no more than a few scattered tumour cells detected by the pathologist in the resection specimen, was used to assess chemosensitivity. RNA was prepared from sections of frozen biopsies taken at diagnosis and hybridised to Affymetrix X3P microarrays. In-vitro single-agent drug sensitivity signatures were combined to obtain FEC and TET regimen-specific signatures. This study is registered on the clinical trials site of the US National Cancer Institute website阅读本文的人还阅读：
作者:admin@医学,生命科学 2011-03-04 05:11
医学,生命科学网