Wang Changjun, Zhu Hanjiang, Zhou Yidong, Mao Feng, Lin Yan, Pan Bo, Zhang Xiaohui, Xu Qianqian, Huang Xin, Sun Qiang
Department of Breast Surgery, Peking Union Medical College Hospital, Beijing, China.
Department of Dermatology, University of California, San Francisco, California.
Breast J. 2017 Jul;23(4):436-443. doi: 10.1111/tbj.12753. Epub 2017 Jan 12.
Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value.
程序性细胞死亡1配体1（PD-L1）是癌症免疫治疗中一个很有前景的治疗靶点。然而，PD-L1与乳腺癌生存率之间的相关性仍不明确。在此，我们进行了首次荟萃分析，以研究PD-L1在乳腺癌中的预后价值。我们在PubMed、Embase和Cochrane对照试验中央注册库数据库中检索了评估PD-L1表达与乳腺癌生存率的相关研究。根据纳入研究的异质性进行固定效应和随机效应荟萃分析。通过漏斗图和Begg检验评估发表偏倚。总体而言，纳入了9项涉及8583例患者的相关研究。在25.8%的乳腺癌患者中发现了PD-L1过表达。PD-L1（+）与多种高危预后指标相关，如导管癌（p = 0.037）、高肿瘤分级（p = 0.000）、雌激素受体阴性（p = 0.000）、孕激素受体阴性（p = 0.000）、人表皮生长因子受体2阳性（p = 0.001）以及侵袭性分子亚型（富含HER2和基底样，p = 0.000）。PD-L1过表达对无转移生存期（风险比0.924，95%置信区间 = 0.747 - 1.141，p = 0.462）、无病生存期（风险比1.122，95%置信区间 = 0.878 - 1.434，p = 0.357）和总体特异性生存期（风险比0.837，95%置信区间 = 0.640 - 1.093，p = 0.191）没有显著影响，但与缩短的总生存期显著相关（风险比1.573，95%置信区间 = 1.010 - 2.451，p = 0.045）。乳腺癌中的PD-L1过表达与多种提示预后不良的临床病理参数相关，并且可能增加死亡风险。有必要进一步规范PD-L1评估检测方法并开展严格控制的临床试验，以阐明其预后和治疗价值。
