Predicting response and survival in chemotherapy-treated triple-negative breast cancer
Predicting response and survival in chemotherapy-treated triple-negative breast cancer
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DOI：
10.1038/bjc.2014.444
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发表时间：
2014-10-14
影响因子：
8.8
通讯作者：
Alba, E.
中科院分区：
文献类型：
--
作者：
Prat, A.;Lluch, A.;Alba, E.
背景资料：在这项研究中，我们评估了基因表达谱的能力，以预测化疗反应和生存在三阴性乳腺癌（TNBC）。方法：基因表达和临床病理数据进行了评估，在五个独立的队列，包括三个随机临床试验，共1055例TNBC，基底细胞样疾病（BLBC）或两者兼而有之。先前定义的内在分子亚型和增殖签名进行了确定和测试。使用多变量逻辑回归模型（对于pCR（病理完全缓解））和考克斯模型（对于生存期）检验每个特征。在TNBC内，每个签名和基底样亚型（相对于其他亚型）之间的相互作用，用于预测pCR或survival.Results：在TNBC内，所有内在亚型被鉴定，但BLBC占主导地位（55-81%）。仅在BLBC中确定了基因组特征与化疗后的反应和生存之间的显著相关性，而在TNBC中未作为一个整体。特别地，发现先前鉴定的增殖特征的高表达或管腔A特征的低表达与pCR独立相关，并且在不同的队列中化疗后存活率提高。显着的相互作用测试，只有每个签名和BLBC亚型之间的预测化疗反应或survival.Conclusions：增殖签名预测化疗后的反应和改善生存，但只有在BLBC。这突出了TNBC异质性的临床意义，并表明未来专注于这种表型亚型的临床试验应考虑将患者分为BLBC或非BLBC。
Background: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC).Methods: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated.Results: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival.Conclusions: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.