三阴性乳腺癌免疫检查点抑制剂的治疗现状与挑战

Current status and challenges of immune checkpoint inhibitors for triple negative breast cancer

目的对免疫检查点抑制剂(ICIs)治疗早期、局部晚期(Ⅰ~Ⅲ期)和晚期(Ⅳ期)三阴性乳腺癌(TNBC)的现状及挑战进行总结。方法以“三阴性乳腺癌、免疫检查点抑制剂、治疗”为中文关键词,以“triple negative breast cancer、immune checkpoint inhibitors、treatment status and challenges”为英文关键词,系统检索中国知网和PubMed数据库2012-12-01-2022-12-31的相关文献。纳入标准:(1)ICIs的发展现状;(2)ICIs对乳腺癌的治疗现状;(3)ICIs对TNBC的治疗现状;(4)TNBC的治疗现状相关文献。排除标准:数据陈旧文献、可信度较低的文献。最终纳入47篇文献进行分析。结果ICIs联合其他治疗如化疗、放疗、靶向治疗等,对早期、局部晚期和晚期TNBC均显示出良好的应用前景,为改善TNBC患者的预后提供了更有效的治疗策略。然而ICIs作为TNBC治疗的新选择,仍存在一些挑战:免疫相关不良事件;程序性死亡配体1(PD-L1)作为主流标志物在预测程序性死亡受体-1(PD-1)/PD-L1 ICIs临床疗效中的局限性;传统的ICIs作为单抗被递送的局限性等。结论ICIs联合化疗、放疗或靶向治疗等在早期、局部晚期和晚期TNBC治疗中虽已取得一定疗效,但仍面临ICIs作为单抗被递送的局限性,以及减少免疫相关不良事件、PD-L1检测方法的缺陷、细胞毒性T淋巴细胞相关蛋白4等其他免疫检查点分子的研究亟待深入等诸多问题的挑战。

Objective To review the current status and challenges of immune checkpoint inhibitors(ICIs)in the treatment of early,locally advanced and advanced triple negative breast cancer(TNBC).Methods With"triple negative breast cancer,immune checkpoint inhibitors,treatment status and challenges as the keywords,PubMed and China National Knowledge Infrastrure(CNKI)databases were systematically searched for relevant literature from 2012-12-01to 2022-12-31.Inclusion criteria were as follows:(1)development status of ICIs;(2)current status of breast cancer treatment with ICIs;(3)current status of TNBC treatment with ICIs;(4)treatment status of TNBC.Exclusion criteria were defined as documents with outdated data and low reliability.Finally,47articles were included for analysis.Results ICIs combined with other therapies,including chemotherapy,radiotherapy,and targeted therapy,showed good application prospects for early,locally advanced,and advanced TNBC,providing a more effective treatment strategy for improving the prognosis of patients with TNBC.However,as a new treatment option for TNBC,ICIs still have some challenges,such as immunerelated adverse events,limitations of programmed death receptor-ligand 1(PD-L1)as a mainstream marker in predicting clinical efficacy of programmed death-1(PD-1)/PD-L1ICIs,and limitations of traditional ICIs delivery method as monoclonal antibodies.Conclusions Although ICIs combined with chemotherapy,radiotherapy,or targeted therapy has achieved certain efficacy in early,locally advanced,and advanced TNBC treatment,there are still some challenges,such as limitations of traditional ICIs delieved as a monoclonal antibody,reduction of immune-related adverse events,deficiencies in PDL1detection methods,urgent need for in-depth research on other immune checkpoint molecules like cytotoxic T lymphocyte associated antigen-4.