TNBC三阴乳癌复习课程.ppt

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1、TNBC的治疗TNBC的治疗生物学：TNBC的分子分型TNBC的预后临床：TNBC的化疗TNBC的靶向治疗乳腺癌的分子分型Her2+Her2-enriched约占45%-60%ER和/或PR+、Her2-、Ki67<14%LuminalA三阴性约占15%，ER-、PR–、Her-2+•IHC3+（>30%的浸润性癌细胞的胞膜呈现完整的强着色）•FISH显示HER2扩增约占15%，ER-/PR/Her2–，与LuminalHER2-enrichedClaudin-lowBasal-likeHER2BasalLuminalProlife

2、rationClaudin3Claudin4Claudin7E-CadherinNormalBreast-likeLuminalBluminal/HER2Basal-like相关联•c-kit、层粘连蛋白、CK5/6高表达，p53及BRCAI突变率高．均为TN型紧密连接蛋白低表达具有干细胞特征和上皮－间质转化(EMT)的特征约占5-10%，•ER+/PR+、Her2-、Ki67≥14%•ER+/PR+、Her2+、Ki67任何水平Basal-likeClaudin-low•••TN中的-75%基底细胞样：CK5/6/17>50%P5

3、3突变•高增殖：Ki-67↑，RB和P53缺失•BRCA1突变•Claudin-low:•均为TN型•紧密连接蛋白低表达•具有干细胞特征和上皮－间质转化(EMT)的特征TNBC的分子分型•Basal-like:TNBCBasal-likeBRCA1上皮间叶转化是癌症发生转移中的一个普遍现象,波形蛋白(Vimentin)蛋白表达上调为其中的一个主要特点PerouC,TheOncologist2011;16(suppl1):61–70.Claudin水平减少•细胞极性失调与肿瘤发生相关•细胞黏附缺失与癌症转移相关乳腺癌的5-10%终生患

4、病风险50-90%Vanderbilt-IngramCancerCenterUNSUnclassifiedBL1Basal-like1BL2IMMBasal-like2ImmunomodulatoryMesenchymalLARLuminal/AndrogenreceptorTNBC的分子分型Cellcycle/DNAreplicationp63/cellcommunicationTGFb/growthfactorsmesencymalMSLMesenchymal/Stem-likeFocalAdhesion/growthfacto

5、rsstemcellAndrogenSignalingTNBC可分为以下6类和1类不稳定型(UNS)基底样1(BL1)基底样2(BL2)免疫调制(IM)间质性(M)间质干细胞样(MSL)Luminal雄激素受体(LAR)BreakdownofTNBCbyMicroarrayDefinedSubtypesasAssignedbyPAM50342tumorswithER,PgR,HER2andmicroarray97basal-like75/97(77%)TNBC22/97(23%)werenotTNBC97TNBC74/

6、97(76%)basal-like23/97(24%)notbasal-likeThereissubstantialoverlapbetweenbasal-liketumorsbymicroarrayandTNBCbyIHCbutapproximately25%ofeithertypearenotconcordant8LumA,4LumB6HER2,5Normal12HER2ParkerJS,etal.JClinOnc2009;27:1160-1167.TNBCSharesClinicalandPathologicFea

7、turesWithBRCA1-RelatedBreastCancers*BRCA1dysfunctionduetogermlinemutations,promotermethylation,oroverexpressionofHMGorID4[4]1.PerouCM,etal.Nature.2000;406:747-752.2.CleatorS,etal.LancetOncol.2007;8:235-44.3.SorlieT,etal.ProcNatlAcadSciUSA.2001;98:10869-10874.4.MiyoshiY

8、,etal.IntJClinOncol.2008;13:395-400.Metzger-FilhoO,etal.JClinOncol.2012;30:1879-1887.Reprintedwithpermission.©(2012)A