三阴性乳腺癌分子分型与个体化靶向治疗现状

目的 三阴性乳腺癌(triple-negative breast caner,TNBC)异质性大,恶性程度高,预后差,对内分泌治疗及抗HER2治疗均不敏感.本研究总结TNBC的分子分型及靶向治疗的临床研究进展,以明确TNBC靶向治疗的研究现状和前景.方法 应用PubMed及CNKI数据库检索系统,以"TNBC、分子分型、和靶向治疗"等为关键词,检索2011-04-2016-04的相关文献.纳入标准:TNBC的分型与靶向治疗.根据纳入标准,最后纳入分析66篇文献.结果 根据基因表达谱,TNBC可分为多种分子亚型,主要为"基底细胞样亚型、间充质/间充质干细胞亚型、免疫调节亚型、管腔雄激素受体亚型".TNBC主要的靶向治疗方式分为5大类:针对DNA修复缺陷的靶向药物、酪氨酸激酶抑制相关的靶向药、PI3K-AKT-mTOR通路抑制剂、免疫检查点抑制剂和雄激素受体抑制剂.其中PARP抑制剂、铂类、PD-L1抑制剂、AKT抑制剂的研究均已进入Ⅲ期临床试验;酪氨酸酶抑制相关靶向药物及PI3K/AKT/mTOR通路抑制剂单药使用的价值有限,可能更适宜多药联合或与传统化疗药物联合应用;雄激素受体抑制剂的治疗价值尚需进一步临床试验的验证.结论 TNBC有多种分子亚型,多种靶向治疗药物处于临床研究阶段,其中PARP抑制剂、铂类、PD-L1抑制剂最具有研究前景.

Triple-negative breast cancer: Molecular subtypes and individual targeted therapies

OBJECTIVE Triple-negative breast cancer (TNBC) is a heterogeneous disease of high malignancy and poor prognosis, which is not sensitive to endocrine therapy and anti-HER2 targeted therapy.The aim of this study is by summarizing molecular subtypes and clinical researches about targeted therapies of TNBC, to make a clear direction of the current development and promising research.METHODS The literature was retrieved in Pubmed and CNKI from April 2011 to April 2016.The key words were triple-negative breast carcinoma, molecular subtype and targeted therapy.The inlcusion criteria: literature about TNBC subtypes and targeted therapies.Sixty-six representative papers were chosen for the review.RESULTS Depending on gene expressing profile, TNBC is divided into several main subtypes: basal-like subtype, mesenchymal/mesenchymal stem-like subtype, immunomodulatory subtype and luminal androgen receptor subtpye.TNBC targeted therapies are summarized into five categories: therapies tageting DNA repair defects, tyrosine kinase inhibition related targeted therapies, PI3K-AKT-mTOR pathway ihibitors, immune checkpoint inhibitors and androgen receptor inhibitors.PARP inhibitors, platinum, PD-L1 inhibitors and AKT inhibitors have being tested in Ⅲ stage clinical trials.Tyrosine kinase ihibition related drugs and PI3K/AKT/mTOR pathway inhibitors seem to be more effective combined with other targeted drugs or traditional chemotherapies than monotherapy.Treatment value of androgen receptor inbihitors are still waiting for validation with further trials.CONCLUSION TNBC have several molecular subtypes, and many targeted drugs are under clinical researches, in which, PARP inhibitors, platinum and PD-L1 inhibitors are the most promising.