06 Paul E. Goss. Optimizing Endocrine Therapy for HR Breast Cancer

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1、13thCBCC&9thSIBCSOctober24th2014ShanghaiChina.OptimizingEndocrineTherapyforHR+BreastCancerPaulE.Goss,MD,PhD,FRCPC,FRCP(UK)ProfessorofMedicine,HarvardMedicalSchoolDirectorofBreastCancerResearchMassachusettsGeneralHospitalCancerCenterCo-DirectoroftheBreastCanc

2、erDiseaseProgram,DF/HCCHR+BCBiologicPathwaysandTreatmentsEstrogensignallingpathwayAlternatecellEstrogensignallingpathwaysGrowthfactorOophorectomOophorectomreceptorligandyyGRB2AromataseAromataseinhibitorsinhibitors(AIs)(AIs)RAS••NonsteroidalNonsteroidalAIsAIs

3、SOSShc−−AnastrozoleAnastrozoleCytoplasm−−LetrozoleLetrozoleRAFPI3K••SteroidalSteroidalAIsAIs−−ExemestaneExemestaneMEKEstrogenAkt/m‐TORreceptorMAPKProliferationApoptosisEstrogenEstrogenreceptorreceptordownregulatordownregulator((ERD)ERD)••FulvestrantFulvestra

4、ntPSelectiveSelectiveestrogenestrogenreceptorreceptorNucleusCofactorcomplexmodulatorsmodulators(SERMs)(SERMs)LBD•TamoxifenLBD•TamoxifenEstrogenPP••ToremifeneToremifeneResponseAF1DBDElementAF1DBDCellgrowthAdaptedfromYardleyDA,etal.JClinOncol.2011;29(suppl27).

5、Abstract268.HR+EarlyBreastCancerOXFORDEBCTCG*EarlyBreastCancerTrialists’CollaborativeGroup,Lancet2011:378:771-84.RichardG.GrayMAMScJClinOncol31,2013(suppl;abstr5)AdaptedofAscoPresentation,2013PostmenopausalAdjuvantTherapy:AIOGMeta-analysis:AIsvsTamoxifenDows

6、ettMetal.JClinOncol.2010Jan20;28(3):509-18.Cohort1*:Tamvs.AI*BIG1-98/ATACCohort2*:Tamvs.SwitchRecurrenceTamAIsRecurrenceTamAIs5years12.6%9.6%3years8.1%5%8years19.2%15.3%6years16.1%12.6%Log-rank2P<.00001Log-rank2P<.000011.Conclusions:*Fourtrials:1.GermanABCGA

7、rimidex-Nolvadex2.AIssignificantlylowerrecurrenceratesvs.tamoxifen2.BIG02-97ExemestaneStudy3.ItalianTamoxifenAnastrozoleTrial(ITA)3.ReductioninMortalityinUp-FrontCohort(BIG1-984.ABCSGVIII)IPCW))4.Noincreaseinnon–breastcancerdeathsforAIsDFS94%AnastrozoleN=7,2

8、001mg/dayx5years•NCICCTGMA.27MedianFollow-upStratifiedHR:1.02(0.87-1.18)4.1years•PostmenopausalER+veExemestanep=0.85EarlyBreastCancer25mg/dayx5years•PrimaryObjective:Eventfreesurvival:AvsEGossPe