乳腺癌的新辅助治疗.ppt

OPENISSUESINMULTIDISCIPLINARYBREASTCANCERMANAGEMENTMediterraneanSchoolofOncologyRome,March30,2012,NEOADJUVANTTHERAPY,LuciaMentucciaOncologiaMedica,Sora,ToimprovesurgicaloutcomesandoptionsForoperablebreastcancer,theaimistoincreasethechanceofbreastconservingsurgeryinpatientswhowouldotherwiserequiremastectomyForinoperablelocallyadvancedbreastcancers,theaimistoachieveoperabilityTogaininformationontumorresponseTodefineshort-termsurrogatemarkersofresponse,GoalsofNeoadjuvantTheapyinBreastCancer,1523ptswithclinicalT1-3,N0-N1breastcancer,Stratification,Age,ClinicalTumorSize,ClinicalNodalStatus,Operation,Operation,NSABPB-18,WolmarkNtal;JNatlCancerInstMonogr.2001,ACx4,ACx4,36%,20%,43%,cCR(249pts),cPR(296pts),cSD+cPD(140pts),23%,4%,9%,pInv(160pts),pNon-Inv(26pts),pCR(63pts),NSABPB-18:ClinicalandPathologicBreastTumorResponse,WolmarkNtal;JNatlCancerInstMonogr.2001,NSABPB-18:SurgeryPerformed,100,80,60,40,20,0,%,P2cm(N=417),BC,breastcancer;FEC,5-fluorouracil,epirubicinandcyclophosphamide*Locallyadvanced=T23,N23,M0orT4ac,anyN,M0;operable=T23,N01,M0;inflammatory=T4d,anyN,M0H,trastuzumab;P,pertuzumab;T,docetaxel,GianniLetal.SABCS2010,H,trastuzumab;P,pertuzumab;T,docetaxel,NeoSpherepCRrates:ITTpopulationsummary,50,40,30,20,10,0,TH,THP,HP,TP,pCR,%95%CI,29.0,45.8,16.8,24.0,6,GianniLetal.SABCS2010,0,10,20,30,40,50,60,70,TH,THP,HP,TP,20.0,26.0,17.4,36.8,29.1,30.0,63.2,5.9,pCR,%95%CI,H,trastuzumab;P,pertuzumab;T,docetaxel,GianniLetal.SABCS2010,NEOSPHERE:pCRandhormonereceptorsstatus,L:lapatinib;T:trastuzumab;L+T:lapatinibplustrastuzumabpCRpathologiccompleteresponseHR:hormonereceptors,pCRbyhormonereceptorstatus,BaselgaJetal.SABCS2010,T:trastuzumab;L:lapatinib;T+L:trastuzumabpluslapatinib,CHER-LOB:pCRratebyHR,HORMONERECEPTORSTATUSANDpCR,NeoadjuvanttherapyinHER2+operablebreastcancer:KeyFindings,PatientselectionismandatoryfortheintegrationofnovelagentsincancertreatmentChemotherapy+trastuzumabisthegoldstandardDouble-HER2blockadeincreasesthepCRrateEndocrinepathwayisstillimportanteveninpresenceofHER2co-expressionThepreoperativesettingisidealtotestnewcombinationsthroughthe“windowofopportunitymodel”,ShouldneoadjuvantregimensforHER2-positivediseasealwayscontainanti-HER2drug?,YesNoA,IsdualHER2-targetingareasonableoptionforthepreoperativesettingforHER2disease?,YesNoA,8.5%,87.2%,4.3%,67.4%,21.7%,10.9%,NeoAdjuvantSystemicTherapy,StGallen2011,VonMinckwitzG,SABCS2010,VonMinckwitzG,SABCS2010,VonMinckwitzG,SABCS2010,OBJECTIVES,VonMinckwitzG,SABCS2010,VonMinckwitzG,SABCS2010,CHARACTERISTICSOFPATIENTS,VonMinckwitzG,SABCS2010,NeoadjuvantBevacizumabandAnthracycline-TaxaneBasedChemotherapyin684TripleNegativePrimaryBreastCancers:SecondaryEndpointAnalysisoftheGEPARQUINTOStudy(GBG44),GerberBetal.ProcASCO2011;Abstract1006.,GerberBetal.ProcASCO2011;Abstract1006.,GerberBetal.ProcASCO2011;Abstract1006.,GEPARQUINTO:BenefitofBevacizumabAddedtoNeoadjuvantChemotherapyinTNBCSubgroup,GerberBetal.ProcASCO2011;Abstract1006.,BenefitofbevlimitedtoTNBCsubgrouppCRbreast(withbevvswithoutbev)*TNBCpatients:36.4vs27.8%(p=0.021)Allpatients:15.0vs17.5%(p=NS),*pCRbreast=noinv/non-invinbreastandnodes,GerberBetal.ProcASCO2011;Abstract1006.,TheEffectofpCRofBevacizumaband/orAntimetabolitesAddedtoStandardNeoadjuvantChemotherapy:NSABPProtocolB-40,BearHDetal.ProcASCO2011;AbstractLBA1005.,BearHDetal.ProcASCO2011;AbstractLBA1005.,NSABPB-40:ChemotherapyBevacizumabinPatientswithOperableHER2-NegativeBreastCancer,OperableBreastCancer,R,TissueforBiomarkers,SURGERY,TissueforBiomarkers,+/-,+/-,X10,NSABPB-40:BenefitofAddingBevacizumabtoStandardChemotherapy,BearHDetal.ProcASCO2011;AbstractLBA1005.,BenefitofbevpredominantinHR+andnotTNBCpatientsubgrouppCRbreast(withbevvswithoutbev):HR+patients:23.3vs15.2%(p=0.008)TNBCpatients:51.3vs47.3%(p=0.44),YesNoA,IfYES,forwhichduration(chooseone)?,2.2%,97.8%,0%,NeoAdjuvan