摘要
目的三阴性乳腺癌(triple-negative breast cancer,TNBC)是一种异质性疾病,恶性度高、预后差,目前缺乏有效的靶向治疗手段。本研究探讨基于基因表达谱、蛋白组学、免疫学和免疫组织化学等不同方法学的TNBC亚分型,旨在明确TNBC亚分型研究现状以及每种亚型潜在的靶向治疗方法。方法应用PubMed及CNKI检索系统,以"三阴性乳腺癌、分型、亚型"为关键词,检索2009-2019相关文献。纳入标准:TNBC的亚分型研究。最终分析符合纳入标准的文献23篇。结果基于基因表达谱、蛋白组学、免疫学、标志物的免疫组织化学分析等信息,TNBC被分为不同的亚型,包括管腔雄激素受体型(luminal androgen receptor,LAR)、基底样型(basal-like,BL)、间充质型(mesenchymal,MES)以及免疫调节型/免疫激活型(immunomodulatory/basal-like immune-activated,IM/BLIA)等,这些亚型表现出不同的生物学及临床特征,提示不同亚型可能对不同的靶向治疗敏感。如LAR对AR拮抗剂敏感,BL可能对铂类化疗药及PARP抑制剂敏感,MES可能对抑制上皮-间质转化相关通路以及抑制肿瘤干细胞相关通路的药物敏感,而IM/BLIA可能会获益于免疫检查点治疗。结论 TNBC具有很大的异质性,明确其亚分型对于理解TNBC的肿瘤生物学特征和临床行为具有重要意义,为将来TNBC患者分层和个体化治疗研究提供了重要依据。
OBJECTIVE Triple-negative breast cancer(TNBC)is a heterogeneous disease with high malignancy and poor prognosis.Currently,there is no effective targeted therapies.This study provided a comprehensive review of TNBC subtyping studies based on different methodologies such as gene expression profiles,proteomics data,immunology information and IHC analysis with the aim to clarify the current status of TNBC subtyping study and potential targeted therapies for each subtype.METHODS The PubMed and CNKI databases were searched by using the keywords triple-negative breast cancer,classification,and subtypes from 2009 to 2019 to identify relevant studies.Inclusion criteria:studies about TNBC subtypes.Twenty-three representative studies were included in this review.RESULTS Based on gene expression profiles,proteomics data,immunology information,or IHC analysis for surrogate markers,TNBC is divided into distinct subtypes including luminal androgen receptor(LAR)subtype,basal-like(BL)subtype,mesenchymal(MES)subtype,immunomodulatory(IM)/basal-like immune-activated(BLIA)subtype,etc.These subtypes exhibit diverse biological and clinical features,suggesting different subtypes of TNBC may be responsive to different targeted therapies.LAR is likely sensitive to AR antagonists.BL may be sensitive to platinum-based chemotherapeutics and PARP inhibitors.MES may be sensitive to agents that inhibited epithelial-to-mesenchymal transition(EMT)-related pathways and tumor stem cell-associated pathways,while IM/BLIA may benefit from immune checkpoint treatment.CONCLUSIONS TNBC is a disease of great heterogeneity.Clarifying TNBC subtypes is important for understanding its biological characteristics and clinical behavior.It also provides an important basis for future TNBC patient stratification and personalized therapies development.
作者
陈琳
罗斌
CHEN Lin;LUO Bin(School of Medicine,Tsinghua University,Beijing100084,P.R.China;Department of General Surgery,Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University,Beijing102218,P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2020年第20期1683-1690,共8页
Chinese Journal of Cancer Prevention and Treatment
基金
北京市卫生系统高层次卫生技术人才培养计划(2013-2-032)。
关键词
三阴性乳腺癌
分型
基因表达谱
蛋白组学
免疫学
免疫组织化学
综述文献
triple-negative breast cancer
subtypes
gene expression profiles
proteomics
immunology
immunohisto-chemistry
review literature
