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ID:16537180
大小:1.91 MB
页数:49页
时间:2018-08-22
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1、InPursuitofPersonalizedTherapyforBreastCancer:GeneExpressionSignaturesJaneS.Chawla,M.D.November6,2009ObjectivesCase:ChemotherapyorNOTWhoshouldreceiveadjuvantchemotherapy?Thebirthofgene-expressionsignatures:IntrinsicbreastcancersubtypesGeneExpressionSignaturesunderdevelopment70-geneS
2、ignature21-geneSignature2-geneSignature50-genesignatureCaserevisitedShouldthepatientreceivechemotherapy?ClinicalCase30y/oWFwithnewlydiagnosedIDCRbreastMMG/Ultrasound1.2x1.2cmmassat10o’clock+surroundingmicrocalcifications+severalsuspiciousaxillaryLNss/pbilateralmastectomiesatOSHSurg
3、icalPath-4.6cmlesionconsistingofIDCmixedwithDCIS;intermediategrade;+lymphovascularinvasion;11(-)LNs;ER+/PR+/HER-2-;T2N0M0OncotypeDX-->lowriskforrecurrenceBasedononcotyperesultsheroncologistrecommendedadjuvanttamoxifenx5yearsPtpresentsforasecondopinionHowelsecanwedifferentiatethesetu
4、mors?WhoShouldReceiveAdjuvantChemotherapy?65%ofwomenwithinvasivebreastcancerhaveLN(-)diseaseAdjuvantchemotherapyimprovesDFSandOSinpre-andpostmenopausalwomen<70withLN+/-breastcancerNSABPB-14&B-20showedthebenefitoftamoxifen&chemoinER+/LN-breastcancerLikelihoodofdistantmetsat10yearsisa
5、bout15%85%ofptsareovertreatedifchemogiventoallpatientsThosewithpoorprognosticfeaturesbenefitmostfromchemotherapyMainclinicalprognosticfactors:age,tumorsize,axillaryLNstatus,tumorhistology,grade,andhormone-receptorstatusSotiriou,C.etal.NEJM,2009.LuminalALuminalBHER2+Basal-likeIntrins
6、icBreastCancerSubtypesdescribedbyPerouetal.Express↑amountsOfluminalcyto-Keratins&geneticMarkersofluminalEpithelialcellsofNormaltissueExpress↑levelsofEGFR,c-kit,&growthfactorslikehepatocytegrowthfactorandIGFGeneExpressionProfilesor“Signatures”Composedofaselectionofgenesfelttoprovidep
7、rognosticorpredictiveinformationabouttumorsAnumberofgeneexpressionsignatureshavebeendevelopedtohelpidentifythosepatientsathighestriskforrecurrentdiseaseThismayavoidchemotherapyadministrationtopatientsatlowriskThe70-geneAssay:MammaPrintMammaprint:Developmentofthe70-GeneSignatureDNAmi
8、croarrayanalysisof7
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