乳腺癌的分子分型

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361004350014R737.9B1001-5930201201-0098-031。、。。11.1NCI1999。。1.2Perou12000luminalsubtype、basal-likesubtype、2humanepidermalgrowthfactorreceptor-2HER-2、HER-2over-expres-sionsubtypenormalbreast-likesubtype。2003Sorlie2AB/C。Perou、Sorlie。、、。estrogenreceptorER、progester-onereceptorPRHER-24luminalA、luminalB、HER-2basal-like。basal-likeER、PR、HER-2。22.1luminalALuminalAERPRHER-2Ki67。44.5%~69.0%3。CK8/18Badve4luminalAForkhead-boxA1FOXA184%。FOXA1luminalA1。luminalA40%ER。HER-2。51824luminalA25.9%、10.3%348.1%~62.5%25.0%~40.0%P<0.05luminalA。2.2HER-2HER-2ER、PRHER-2Ki-67。HER-2+++FISH。20%~30%HER-2。。HER-2ERBB217TRAP100、GRB76~11RRM2、RAD5。ER、PR。。HER-2HER-2。trastuzumab1HER-2FDA1998HER-2。HER-2。Slamon12、Marty13。、、。。Konecny14。lapatinib1EGFRHER-22007FDAHER-2·89·20121271ThePracticalJournalofCancerJanuary2012Vol27No.1。。NSABPB-31、HERA50%15~172006FDAHER-2。2.3luminalBluminalBERPRHER-2。HER-2lu-minalA。18luminalB88%。HER-2。2011NCCN>1cm、1、0.6~1cm、23、±1±3≤0.5cm0.6~1cm、1、≤2mm。2.4basal-like1。ER、PR、HER-2basal-like5%~45%ER1914%HER-22080%~90%basal-like19。Nielsen21ER、HER-2CK5/6、CK14、CK171EGFR。。CK5/6basal-like。47~55。basal-like18.9%~28.8%22~24CK5/6、CK14vimentin85%p5360%EGFR25、、、。1、。HER-2。EGFR、MAP。dasatinib1BCR-ABLSRCbasal-like2627。basal-likeEGFRbevacizumab2829。2.5normalbreast-likeNormalbreast-likeER、HER-2CK5/6、CK14、CK17、EGFR。。。。1CER、PRHER-2。HER-2HER-2。C。VanCalster30。HER-2。HER-231。。“、”。1PerouCMSorlieTEisenMBetal.Molecularportraitsofhumanbreasttumors〔J〕.Nature20004066797747.2SorlieTTibshiraniRParkerJetal.Repeatedobservationofbreasttumorsubtypesinindependentgeneexpressiondatasets〔J〕.ProcNatlAcadSciUSA2003100148418.3.〔J/CD〕.200932195.4BadveSTurbinDThoratMAetal.FOXA1expressioninbreastcancer-correlationwithluminalsubtypeAandsurvival〔J〕.ClinCancerRes20071315Pt14415.5.〔J〕.2009364199.6BockerWMollRPorembaCetal.Commonadultstemcellsinthehumanbreastgiverisetoglandularandmyoepithelialcelllineagesanewcellbiologicalconcept〔J〕.LabInvest2002826737.7BoeckerWBuergerH.Evidenceofprogenitorcellsofglandularandmyoepithelialcelllineagesinthethehumanadultfemalebreastepi-theliumanewprogenitoradultstemcellconcept〔J〕.CellProlif200336Suppl173.8StinglJEavesCJZandiehIetal.Characterizationofbipotentmam-maryepithelialprogenitorcellsinnormaladulthumanbreasttissue〔J〕.BreastCancerResTreat200167293.·99·20121271ThePracticalJournalofCancerJanuary2012Vol27No.19DontuGAbdallahWMFoleyJMetal.Invitropropagationandtranscriptionalprofilingofhumanmammarystem/progenitorcells〔J〕.GenesDev200317101253.10DontuGAlHajjMAbdallahWMetal.Stemcellsinnormalbreastdevelopmentandbreastcancer〔J〕.CellProlif200336Suppl159.11BirnbaumDBertucciFGinestierCetal.Basalandluminalbreastcancersbasicorluminous〔J〕.IntJOncol2004252249.12SlamonDJLeyland-JonesBShakSetal.UseofchemotherapyplusamonoclonalantibodyagainstHER2formetastaticbreastcancerthatoverexpressesHER2〔J〕.NEngJMed200134411783.13MartyMCogneticFMaraninchiDetal.RandomizedphaseIItrialoftheefficacyandsafetyoftrastuzumabcombinedwithdocetaxelinpatientswithhumanepidermalgrowthfactorreceptor2-positivemeta-staticbreastcanceradministeredasfirst-linetreatmenttheM77001studygroup〔J〕.JClinOncol200523194265.14KonecnyGEPegramMDVenkatesanetal.Activityofthedualki-naseinhibitorlapatinibGW572016againstHER-2-overexpressingandtrastuzumab-treatedbreastcancercells〔J〕.CancerRes20066631630.15RomondEHPerezEABryantJetal.Trastuzumabplusadjuvantc-hemotherapyforoperableHER-2-positivebreastcancer〔J〕.NEnglJMed2005353161673.16PiccartGebhartMJProcterMLeylandJonesBetal.TrastuzumabafteradjuvantchemotherapyinHER-2-positivebreastcancer〔J〕.NEnglJMed2005353161659.17JoensuuHKellokumpuLehtinenPLBonoPetal.Adjuvantdocet-axelorvinorelbinewithorwithouttrastuzumabforbreastcancer〔J〕.NEnglJMed20063548809.18EllisMJCoopASinghBetal.Letrozoleismoreeffectiveneoadju-vantendocrinetherapythantamoxifenforErbB-1-and/orErbB-2-positiveestrogenreceptor-positiveprimarybreastcancerevidencefromaphaseⅢrandomizedtrial〔J〕.JClinOncol200119183808.19RakhaEAEl-sayedMEGreenARetal.Prognosticmarkersintri-ple-negativebreastcancer〔J〕.Cancer2007109125.20RouzierRPerouCMSymmansWFetal.Breastcancermoleculars-ubtypesresponddifferentlytopreoperativechemotherapy〔J〕.ClinCancerRes200511165678.21NielsenTOHsuFDJensenKetal.Immumohistochemicalandclini-calcharacterizationofthebasal-likesubtypeofinvasivebreastcarci-noma〔J〕.ClinCancerRes200410165367.22.〔J/CD〕.200932139.23.〔J〕.2009316447.24.〔J〕.2009304458.25SavageKLeungSToddSKetal.Distributionandsignificanceofcaveolin2expressioninnormalbreastandinvasivebreastcanceranimmunofluorescenceandimmunohistochemicalanalysis〔J〕.BreastCancerResTreat20081102245.26FinnRSDeringJGintherCetal.Dasatinibanorallyactivesmallmoleculeinhibitorofboththesrcandablkinasesselectivelyinhibitsgrowthofbasal-type/triple-negativebreastcancercelllinesgrow-inginvitro〔J〕.BreastCancerResTreat20071053319.27DizdarODedeDSBulutNetal.Dasatinibmayalsoinhibitc-Kitintriplenegativebreastcancercelllines〔J〕.BreastCancerResTreat20081072303.28MillerKWangMGralowJetal.Paclitaxelplusbevaci-zumabver-suspaclitaxelaloneformetastaticbreastcancer〔J〕.NEnglJMed2007357262666.29Mill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