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[乳腺癌中的程序性死亡受体配体1(PD-L1)表达及程序性死亡蛋白1(PD-1)/程序性死亡受体配体1(PD-L1)抑制剂]

[PD-L1 expression and PD-1/PD-L1 inhibitors in breast cancer].

作者信息

Monneur Audrey, Gonçalves Anthony, Bertucci François

机构信息

Institut Paoli-Calmettes, département d'oncologie médicale, 232, boulevard de Sainte-Marguerite, 13009 Marseille, France.

Institut Paoli-Calmettes, département d'oncologie médicale, 232, boulevard de Sainte-Marguerite, 13009 Marseille, France; Aix-Marseille université, centre de recherche en cancérologie de Marseille, Inserm U1068-CNRS U7258, 232, boulevard de Sainte-Marguerite, 13009 Marseille, France; Aix-Marseille université, 13009 Marseille, France.

出版信息

Bull Cancer. 2018 Mar;105(3):263-274. doi: 10.1016/j.bulcan.2017.11.012. Epub 2018 Feb 16.

Abstract

The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing). Its prognostic value remains controversial when assessed with immunohistochemistry, whereas it seems favorable in triple-negative cancers when assessed at the mRNA level. Early clinical trials with PD-1/PD-L1 inhibitors in breast cancer have shown efficacy in terms of tumor response and/or disease control in refractory metastatic breast cancers, notably in the triple-negative subtype. Many trials are currently underway, both in the metastatic and neo-adjuvant setting. A crucial issue is identification of biomarkers predictive of response to PD-1/PD-L1 inhibitors.

摘要

免疫检查点抑制剂的研发是肿瘤学领域近年来的重大进展之一。针对程序性细胞死亡蛋白1(PD-1)或其配体(PD-L1)的单克隆抗体可实现持久的疾病控制,尤其是在黑色素瘤、肺癌、肾癌、膀胱癌以及头颈癌中。本综述的目的是综合目前关于乳腺癌中PD-L1表达以及PD-1/PD-L1抑制剂在乳腺癌患者中的初步临床结果的数据。在乳腺癌中,PD-L1表达具有异质性,通常与肿瘤浸润淋巴细胞的存在以及不良预后因素有关,如年轻、高级别、雌激素受体阴性、孕激素受体阴性、HER-2过表达、高增殖指数以及侵袭性分子亚型(三阴性、基底样、HER-2过表达型)。通过免疫组化评估时,其预后价值仍存在争议,而在mRNA水平评估时,它在三阴性癌症中似乎具有预后优势。PD-1/PD-L1抑制剂在乳腺癌中的早期临床试验已显示出对难治性转移性乳腺癌,尤其是三阴性亚型,在肿瘤反应和/或疾病控制方面具有疗效。目前,许多转移性和新辅助治疗的试验正在进行。一个关键问题是识别预测对PD-1/PD-L1抑制剂反应的生物标志物。

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