劉健(英文)：后人工智能時(shí)代晚期癌癥內(nèi)分泌治療策略

TheTreatmentStrategyintheEndocrineTherapyofAdvancedBreastCancerinPostAIEra

JianLiu

ContentsStatusandthepresentsituationofETinAdvancedBCsPrincipleofETandthetreatmentchoicepostAIEraExplorationofbiomarkersthatguidedETContentsStatusandthepresentsituationofETinAdvancedBCsPrincipleofETandthetreatmentchoicepostAIEraExplorationofbiomarkersthatguidedETMainobjectiveofadvancedBCstherapyAdvancedBCscannotbecured,balancingthesafetyandefficacyarethemainobjective.Therapeuticgoals:Improvement

in

overall

survival

(Lessdrugscouldachievedthis)DelaytheprogressionofdiseaseExtendthetreatmentbenefitdurationRelievethesymptomsImproveorremainthequantityoflifeTransformtochronicdiseasesQuantityofLifeQualityofLifeETandChemotherapyhaveequivalenteffort-OSDirectcomparison:NosignificantlydifferenceinOSWilckenetal.,CochraneDatabaseSystRev,2009.Authoritativeguidelinesrecommend：

ETisthefirstchoiceforER+advancedBCsAslongaspatientsarehormonesensitive,itshouldbepossibleforthemtoacceptcontinuingendocrinetherapy2Becauseofthechemotherapytoxicity,therightpatientsshouldreceiveextendedETasfaraspossible2ChemotherapycanbeusedonlyifpatientsareresistanttoET21.CardosoF,etal.AnnOncol2011;22(S6):vi25-vi30.2.RobertsonJFR,etal.EurJCancer2005;41:346-356.UnlessthetumorisaprogressiondiseaseandneedquickrelieforitscannotsurewhethertumorissensitivetoET，

ETisthefirstchoiceforER+advancedBCpatients.1HowdidEuramericanphysicianstreatER+/HER2

negativepatients?ThesestudiesrevealedthatEuramericanphysicians

usuallychooseothertypesoftherapyonlywhenadvancedBCspatientshavenobenefitsoffirst/secondlineET.1.SwallowE,etal.CurrMedResOpin2014;30:1537-1545;2.AndreF.etal.CurrMedResOpin2014;30:1007-1016AnalysisER+/HER2

NumberProportionofadvancedfirstline

PercentageofETaccounted

FirstlineSecondline>=ThirdlineUS11912060%44%12%4%Europe236569%62%7%0%60-70%ofER+ABCpatientsreceivedfirstlineETChina：Of139bonemetastaticHR+patients，28.8%choseET，themedianOSis61months1Korean：Of146bonemetastaticpatients(85%HR+,8.2%HER2+,6.8%TN),45.9%choseET，HR+populationpatientsmedianOSis65months21.XuBingheetalChinaMedicalJournal

2012;92:3279-3282.2.LeeSJetalCancerResTreat.2011,43:89-95Firstlinechemotherapy(%)FistlineET(%)DatafromChinaTheproportionoffirstlineETinER+bonemetastatic

advancedBCsisrelativelow.TheproportionofETinChinaislessthanthatinKoreanContentsStatusandthepresentsituationofETinAdvancedBCsPrincipleofETandthetreatmentchoicepostAIEraExplorationofbiomarkersthatguidedETERAF2AF1EestradiolCo-activator2EREAF1EEAF2AF2AF1Co-activatior1RNA-PolyI轉(zhuǎn)錄Co-Repressor2Co-Repressor1AF1EEAF2AF2AF1HSP90Frommolecularmechanismtodiscussion-EstrogenreceptorpathwayPeterSchmidpresentedatFulvestrant500mglaunchmeetinginShanghai2015.TranscriptionEEREREEREREEEEstrogenEFPre-menopause:GnRHactivator(+/-AI)Post-menopause:AISERMTAMSERDFulvestrant?ThemechanismofETPeterSchmidpresentedatFulvestrant500mglaunchmeetinginShanghai2015.EstradiolHOOHFulvestrantHOOH(CH2)9SO(CH2)3CF2CF3Fulvestrant?mechanism-HighsimilarityinchemicalstructureFulvestrant?competeswithestrogeninbindingER,withaffinityto89%,whichissignificantlyincreasedcomparedwithTAM.ONMe2TAMOsborneCKetal.BritishJournalofCancer(2004)90(Suppl1),S2-S6ERAF2AF1TAMTAF1AF2AF2AF1TTEREAF1AF2AF2AF1Co-activator1RNA-PolyICo-repressor1TTTranscriptionchangeERAF2AF1芙仕得?FAF1AF2FAF1AF2FAF1AF2FERERNA-PolyIAF1AF2FER

genetranscriptionPeterSchmidpresentedatFulvestrant500mglaunchmeetinginShanghai2015.Fulvestrant

vs.TAMFulvestrant?-thefirstandtheonlyoneERrepressorItcouldbind,block,reduceanddegradeERTheuniquemechanism-

Howtotransforminclinical？HowtoestimateFulvestrantreduceanddegradeERinclinicalpractices？

HowtopredictFlulvestranteffect？CancerDiscov，IF19.4

UsingFES-PETtomeasuringERvariationduringfulvestranttherapy:BackgroudvanKruchtenM,etal.CancerDiscov2015;5(1):72-81.對于大部分轉(zhuǎn)移性乳腺癌患者來講,反復(fù)獲取轉(zhuǎn)移灶的標(biāo)本來做ER檢測存在困難.UsingPETandPET/CTwith16α-[18F]-17β-estradiol(FES)tomeasuretheERdistribution,magnitudechangeandavailability.etalinbreastcancertissueandmetastatictissue.EstrogenbindingStudydesignFulvestrant500mgd1,14,28,q4wAdvancedBCsreceivedatleastpriorsecondlinestherapy(TAMandAItreatment)N=16Studyobjective：thecorrelationbetweenFES-PETresults,plasmafulvestrantlevels,andtreatmentoutcome;theheterogeneityofFESuptakeamonglesionsandbetweenindividuals;and(iii)thefeasibilityofquantifyingliverlesionsbyFES-PETvanKruchtenM,etal.CancerDiscov2015;5(1):72-81.SUVdefinedasstandarduptakevalue，referringtoradioactivityofdeveloperuptakenbylocaltissueandtheaverageinjectionactivityofthewholebody.SUVmax≥1.5todefineFESpositive/?tn=98012088_4_dg&ch=12IncompletereductioninERavailabilityinapatientwasdefinedasarelativedecreaseinFESuptakeoflessthan75%inmediantumorlesionSUVcorandanabsolutemediantumorlesionSUVmax>1.5.FES-PETScan,plasmaestrogenlevelsBaselineDay28Day84FirstScanSecondScanThirdScan(CTexaminationmeanwhile)PatientscharacteristicsandeffortcharacteristicNNumberofpatietns16Age,median(range)55(45-72)BMI,kg/m2,

median(+/-SD)24(+/-4)Sex

female16ER+16PR+11HER2+0Boneonly3Bone+visceral(+/-nodes)8Bone+nodes3Visceralonly2PriorlinesofendocrinetherapyTAM,AI14TAM,AI,mesgestrol2Priorlinesofchemotherapy011>=14NumberofPatientsPR1SD8

SDpatients>=24

weeksPD4patientshadradiologicPDand2had

clinicalPD.PD(CA15.3

wasa3-to12-foldincrease)Medial

PFS(range)6.5(1.9-15.9)monthsvanKruchtenM,etal.CancerDiscov2015;5(1):72-81.FES-PET

resulatsAnalysis

類別結(jié)果SUVmax病灶medial(范圍)3.4(1.4-7.4)Day56SecondScan(2patients)FES-PETscan,EstrogenplasmalevelBaselineDay28Day84FirstScan(16

patients)SecondScan(12patients)ThirdScan(9

patients)SecondScan(2

patients)檢測類別結(jié)果中位殘余腫瘤SUVmax(范圍)1.7(1.1-3.8)檢測類別結(jié)果中位殘余腫瘤SUVmax1.6vanKruchtenM,etal.CancerDiscov2015;5(1):72-81.Atthesecondscan,themedianchangeinFESuptakeforthe16patientswas?88%.MedianresidualtumorSUVmaxwas1.7.FES-PET/CTassessmentindicatedfulvestrantreducedtheERlevelintumorsofBCs.Pre-andposttreatmenttumorSUVcorinpatientsvanKruchtenM,etal.CancerDiscov2015;5(1):72-81.Pretreatment(squares)andposttreatment(diamonds)background-correctedtumorFESuptake(SUVcor)forallindividualpatients.Patientsaregroupedaccordingtotheirresponse,inbluepatientswithpartialresponseandSD,andinredpatientswithPD.Intwopatientswithrecenttamoxifentherapy,apreviousbaselinePETwasavailablewhileonaromataseinhibitortherapy.ThegreensquaresanddiamondsrepresentthevaluesifthepreviousPETwouldhavebeenusedasbaselinemeasure.6543210ClinicalbenefitProgressiondiseaseNEPartialresponseStablediseaseProgressivedisease(radiologic)Progressivedisease(clinical)NotevaluablePosttreatmentSUVcorPretreatmentSUVcorCorrecteddatafortamoxifenuse*PriorTAM****9

patientsFESmedialuptake≥75%,8

patients

(89%)achievedclinicalbenefitIndividualpatientsPre-andposttreatmenttumorSUVcorinpatientsFESuptake(SUVcor)inindividualpatientsatthesecondscancomparedwithbaselinevanKruchtenM,etal.CancerDiscov2015;5(1):72-81.*Patientswhousedtamoxifenuntil5weeksbeforebaselinePETareindicated(*).Intwopatientswithrecenttamoxifentherapy,apreviousbaselinePETwasavailablewhileonaromataseinhibitortherapy.TheshadedbarsrepresentthevaluesifthepreviousPETwouldhavebeenusedasbaselinemeasure1007550250-25-50-75-100*****PartialresponseStablediseaseProgressivedisease(radiologic)Progressivedisease(clinical)NotevaluableCorrectedfortamoxifenPriortamoxifenIndividualpatientsChangefrombaseline9

patientsmedialFESuptake≥75%patients，medialPFSis11.7monthsThecorrelationbetweentumorFESuptakeandfulvestrantplasmalevelMedianfulvestrantplasmalevel:day28:33nmol,day8427nmol/lAlthoughmedianfulvestrantlevelswereslightlyhigherinpatientswhohadclinicalbenefitfromfulvestrantcomparedwithpatientswithPD(39.6vs.29.4nmol/L),plasmafulvestrantlevelsdidnotcorrelatewithabsoluteorrelativechangesineitherSUVmaxorSUVcor.vanKruchnM,etal.CancerDiscov2015;5(1):72-81.ConclusionsFESPET/CTinclinicalpracticeindicatedthatfulvestrantreducedERlevels,whichwasdirectcorrelatedwithclinicaleffect.FES/PET-CT

couldidentifydifferentpatientsresponsetofulvestrantmoreaccuratelyviaiconographymanner.NeitherbaselineFESuptakenorfulvestrantplasmaconcentrationcouldpredictbenefitfromtherapy.FESPET/CTnoninvasivelyandrealtimedynamiclymonitoredERchange,andaccuratelypredictedfulvestranteffect,whichprovidedanoptionforprecisiontherapyviafutureiconographyconbiningwithclinicalmedicine.vanKruchtenM,etal.CancerDiscov2015;5(1):72-81.PostAIEra,advancedBCpatientsETchoice--

HowtochoosewhenER+ABC

patientsfailedinAItherapy？？ProgestinTAMFulvestrant500FirstlinetherapyAdjuvanttherapySecondarylinetherapyFulvestrant500SAISAISAITAMNSAIUsedifferenttypesofAIsequentialtherapy

medialTTP3-5

monthMillerWR,etal.BreastCancerRes2012;14:201.InitialTherapySecondarylineNumberORR(%)TTP(m)AnastrozoleorletrozoleExemestane

238.75.1AnastrozoleExemestane

12--4.4AnastrozoleExemestane

508.05.0AnastrozoleorletrozoleExemestane

1145.04.5AnastrozoleorletrozoleExemestane

3119.43.2AnastrozoleorletrozoleExemestane

300.04.0AnastrozoleorletrozoleExemestane

6020.03.2AnastrozoleorletrozoleExemestane

1054.83.2MillerWR,etal.BreastCancerRes.2012Jan19;14(1):201.BOLERO-2：Exemestane

EverolimusPost-menopauseHR(+),HER2(-)advancedBCsProgressionafterpreviousnon-steroidalAItherapy*(n=724)Exemestane

25mg/d+Everolimus

10mg/d(n=485)Exemestane

25mg/d+placebo(n=239)Treatmentuntildiseaseprogressionoroccursun-toleratetoxicityRHierarchicalfactors：SensitivityofpreviousAItherapyWhethersufferedVisceralmetastasisPrimaryEndpoints：PFS(Investigatorassessment)SecondaryEndpoints：ORR、OS、CBR、Safety2:1HortobagyiGN,etal.SABCS2011.AbstractS3-7.BaselgaJ,etal.NEnglJMed2012;366:520-529.BOLERO-2：PrimaryEndpointsBaselgaJ,etal.NEnglJMed2012;366:520-529.0依維莫司+依西美坦(E/N=202/485)安慰劑+依西美坦(E/N=157/239)

everolimus458398294212144108755134188330

placebo2391771097036261614943100Time(week)Numberofpatientsinrisk：01261824303648604254726678HR=0.43(95%CI:0.35–0.54)EVE+EXE:6.9monthsPBO+EXE:2.8monthsLogrankP

=1.4x10-1580604020100事件發(fā)生率(%)2015SABCS:bycfDNAtest,BELERO-2:AfterAItreatment,ESR1mutantratereached28.8%。ESR1-mutantinfluenceOS（non-mutantMST32.1months,mutantMST20.7months，HR=1.40，95%CI1.2-1.65，P=0.000037）DespiteAI

withcombinationofmTOR

inhibitor,poorprognosiscausedbyESR1mutantcannotbeimproved.PFSsubgroupanalysis：

ineverolimuscombinationgroup,themoretimesofprevioustreatment,thegreaterbenefittherewillbe

EVE=依維莫司；EXE=依西美坦；PLB=安慰劑BaselgaJ,etal.NEnglJMed2012;366:520-529.subgroupNo.HR(95%CI)EverolimusbetterPlacebobetterTimesofpriortherapy12

3RecenttherapyAIAnti-estrogenOthersPurposeofRecentTreatmentAdjuvantTherapyPrioreverolimustherapyYesNoPriorchemotherapyYesNeo-adjuvantoradjuvanttherapyonlyTreatmentformetastaticdiseaseNoPRpositiveYesNo118217389532122705861381196053061862325231840.10.30.51.010.0PalliativecareBOLERO-2：

Recommendfulvestrant+exemestaneforpatientswithshorterDFS(nolongerendorinesensitive)

J.ThaddeusBecketal.BreastCancerResTreat(2014)143:459–467.ChinaCONFIRMstudydesignPrimaryendpoints：PFSSecondaryendpoints：ORR,CBR,DOR,DOCB,safety,

PKAO=抗雌激素；DOR=緩解持續(xù)時(shí)間；DOCB=臨床獲益持續(xù)時(shí)間JiangZF,etal.2014SABCSP1-13-07.Fulvestrant500mg(n=111)Fulvestrant

250mg(n=110)PostmenopausalpatientsHRpositiveAdvancedBCsProgressionorrecurrenceafterPriorET(n=221)RRandom,doubleblinded,parallelstudyAccordingAOorAItohierarchy1:1AIsubgroup：Fulvestrant500mg

medial

PFS:5.8months,reducing35%progressionriskMedialPFS:Fulvestrant

500mg5.8monthsFulvestrant

250mg2.9monthsHR0.65;95%CI0.42,1.0300.00.20.40.60.81.03691215182124273033365332232115121086331047201412933321110Fulvestrant

500mgFulvestrant250mgNumberofatientswithriskProgressionfreepatientsrateFromtimetorandomization(months)Fulvestrant

250mgFulvestrant

500mg35%20%-50%ofER+advancedpatientswhoacceptedAItreatmentoccuredESR1mutationLBDmutationofERisamainreasonofacquiredendocrineresistanceESR1mutantafterAItreatmentleadstoacquiredresistanceofAI

FulvestrantisachoiceforER-relatedendocrinetherapyresistanceESR1mutantClusterin“ER

ligandbindingdomain”Activeligand-IndependentEREndocrineResistanceAdvancedMetastasisAbilityJeselsohnR,etal.NatRevClinOncol.2015Jun30.doi:10.1038/nrclinonc.2015.117.FERGI:Fulvestrantmonotherapygroup：PFSofESR1mutationcarriersESR1-mutantdoesnotaffecttheeffectofFulvestrantGendreauS,etal.SABCS2015PD6-03.1.00.80.60.40.20.002468101214161820222426Median，monthHR(95%CI)Log-rankp-valueESRWTESR1MutESR>1MuT

3.77.43.5

0.8881.388(0.471,1.689)(0.671,2.870)0.70860.3746時(shí)間(月)PFSESRWT(N=40)ESR1Mut(N=18)ESR>1MuT(N=12)InpostAIera，endocrinetherapyforadvanceddisease—

Fulvestrantisthefirst-linestandardendocrinetherapyforER+ABCafterfailureofadjuvantAItreatmentProgesteroneTAMFul500mgFirstlineAdjuvantSecondlineFul500mgSAISAISAITAMNSAI2.8monthes5.8monthsProgestogenTAM/NewlyDiagnosedFul500mgNSAISAIFul500mgSAINSAINSAIFirstlineAdjuvantSecondlineInpostAIera，endocrinetherapyforadvanceddisease—

ChoiceforER+newlydiagnosedoradjuvantTAMfailure？FIRST:Studydesign35ER+

post-menopauseABCrandom(1:1)、Openfist-linetreatment

(n=200)PFSfollow-upProgressionFulvestrant500mg(IM0、14

&28

days

500mg28daysrepetition)ProgressionPFSfollow-upAnastrozole1mg(1mg/day，peros)

OSfollow-upOSfollow-upRobertsonJFR,etal.JClinOncol2009;27:4530-4535.RobertsonJFR,etal.BreastCancerResTreat2012;136:503-511.36aInaddition，onepatientoffulvestrantgroupreceivedeatrogentherapyrandomizedwithin12monthsRobertsonJFR,etal.JClinOncol2009;27:4530-4535.BaselinecharacteristicNumberofpatients

(%)Fulvestrant

500mgn=102Aanstrozole

1mgn=103Medianage66

years68yearsStageofdiseaseLocaladvancedonly19(18.6)18(17.5)metastatic83(81.4)85(82.5)Measurablelesion89(87.3)93(90.3)PriorendocrinetherapyPriorreceivednoendocrinetherapy73(71.6)80(77.7)Randomization>12mreceivedendocrinetherapy28(27.5)a23(22.3)PriorreceivedearlyBCsadjuvantchemotherapy29(28.4)25(24.3)Priorreceivedchemotherapyandhormonotherapy19(18.6)13(12.6)Primaryendpoints:higherclinicalbenefitrateinfulvestrantgroupthanAIgroup37CB=ClinicalbenefitRobertsonJFR,etal.JClinOncol2009;27:4530-4535.Clinicalbenefitrate(CB)Fulvestrant

500mg%(Patientsofclinicalbenefit/Totalpatients)Anastrozole1mg%)(Patientsofclinicalbenefit/Totalpatients)Oddsratio(95%CI)p-valueAbsolutedifference(95%CI)72.5%

(74/102)67.0%

(69/103)1.30(0.72，

2.38)0.3865.6%(-7.8%，

15.8%)Alltherandomlyassignedpatients(n=205)Fulvestrant

500mgn=102Anastrozole

1mgn=103Numberofprogressors(%)63(61.8)79(76.7)Mediansurvival(moths)23.413.138LongerPFS(10.3months)infulvestrantgroupthanAIgroupAfterthedeadline，progressionwasdeterminedbyinvestigatorRobertsonJFR,etal.BreastCancerResTreat2012;136:503-511.06121824303642480.00.20.40.60.81.0

RateofPFSpatientsTime(months)102746552453420601036955393021820Fulvestrant

500mgAnastrozole1mgHR=0.6695%CI(0.47,0.92)p=0.01Fulvestrant500mgAnastrozole1mgNumberofriskpatients：012184248

month3630246IIIstageresultsofComparisonofFIRSTandfirst-lineendocine

therapyforABC

SignificantlyLongerTTPwithFulvestrant39FIRST

(n=205)AnaF50013.123.4BonneterreJ,etal.Cancer2001;92:2247-2258.MouridsenH,etal.JClinOncol2001;19:2596-2606.ParidaensRJ,etal.JClinOncol2008;26:4883-4890.RobertsonJFR,etal.BreastCancerResTreat2012;136:503-511.Bonneterreetal.

Cancer

2001

(n=1021)Mouridsenetal.

JClinOncol2001

(n=916)Paridaens

etal.

JClinOncol

2008(n=371)AnaLetExeMedianTTP(month)8.59.49.9TamTamTam7.06.05.8ABC,advancedbreastcancer;Ana,anastrozole;Exe,exemestane;F500,fulvestrant500mg;Let,letrozole;Tam,tamoxifenFul

500mgn=102Ana1mgn=103死亡數(shù)(%)63(61.8)74(71.8)中位總生存期((月)54.148.4OSinFIRST

differsbetweenthegroups:

OSoffulvestrantgroupwas54.1months

andlongerthanAIgroup40RobertsonJFR,etal.BreastCancerResTreat2012;136:503-511.061218243036421080.00.20.40.60.81.0ProportionofSurvivalTimeFul

500mgAnastrozole

1mgHR=0.7095%CI(0.50,0.98)p=0.04148546066727884909610210290847757473124103908072493921140121824364860728496MonFul500mgAna1mg423929PatientsinDanger：Lowerseriousadverseevents(SAE)incidenceinFulvestrantgroup41RobertsonJFR,etal.BreastCancerResTreat2012;136:503-511.NumberofPatients(%)Ful

500mgn=101Ana1mgn=103Seriousadverseevents

AnyType24(23.8)22(21.4)

Non-DeadOutcome21(20.8)18(17.5)

AnyDead-relatedOutcome3(3.0)5(4.9)

AnyAssociatedwithDrug2(2.0)0IIIstageresultsofComparisonofFIRSTandfirst-lineendocinetherapyforABC

SignificantlyLongerOSwithFulvestrant42BonneterreJ,etal.Cancer2001;92:2247-2258.MouridsenH,etal.JClinOncol2001;19:2596-2606.ParidaensRJ,etal.JClinOncol2008;26:4883-4890.RobertsonJFR,etal.BreastCancerResTreat2012;136:503-511.Nabholtz

etal.

EurJCancer2003

(n=1021)Mouridsenetal.

JClinOncol

2003(n=916)Paridaens

etal.

JClinOncol

2008(n=371)AnaLetExeMedianOS(month)39.23437.2FIRST

(n=205)AnaF50048.454.1TamTamTam40.13043.3OngoingIIIStageResearch:FALCON43ProgressionFulvestrant500mg

+placeboOSPost-menopausalmetastaticLuminalBCwithoutprevioushormonetreatmentProgressionOSAnastrozole+PlaceboTTPAnalysiswhenprogressionof306casesOSAnalysiswhendeathrateof50%Random

1:1(n=450)孕酮TAM/NewlyDiagnosedFulvestrant500mgNSAIFirstlineAdjuvantTherapySecondlineSAIFulvestrant500mgSAINSAINSAIStrategiesfortreatmentofpostmenopausalestrogenreceptorpositiveadvancedbreastcancer.FulvestrantisThefirst-linestandardendocrinetherapyfornewlydiagnosedpatientsorafterTAMfailure.23.4months13.1monthsContentsStatusandthepresentsituationofETinAdvancedBCsPrincipleofETandthetreatmentchoicepostAIEraExplorationofbiomarkersthatguidedETResistanceandtheCrosstalkbetweenERandintracellularsignalpathwaysERdeletionESR1mutationsER

ancillarytranscriptionfactororco-activatorsoverexpression2,3Non-genomicERpathwayactivation4EGFRpathwayactivation420%-50%ofER+patientswhoacceptedAItreatmentoccuredESR1mutation,whichmaycausetheactivationofligand-independentpathwaysandleadstoacquiredresistanceofAI1.OesterreichS,DavidsonNE.NatGenet2013;45(12):1415-1416.2.SchiavonGetal.ScienceTranslationalMedicine2015,Vol7Issue313ESR1mutation1ESR1mutationpredictAIresisdence2PFSonAItherapyafterctDNAanalysisforpatientswithESR1mutantandWTctDNA(HR,3.1;95%CI,1.9to23.1;P=0.0041,log-ranktest).ESR1mutanthappensmostlyinpatientswithvisceralmetastases,secondaryresistanceofAI,morethan2metastaticlesions,PIK3CAmutantorLuminalA

typeGendreauS,etal.SABCS2015PD6-03.ESR1wt96(62.7%)ESR1mt57(37.3%)Total153(100%)No.ofESR1mutation096(100%)096(62.7%)1034(59.6%)34(22.2%)2013(22.8%)13(8.5%)3+010(17.5%)10(6.5%)VisceraldiseaseYes45(46.9%)35(61.4%)80(52.3%)No51(53.1%)22(38.6%)73(47.7%)PriorAIresistancePrimary42(43.8%)15(26.3%)57(37.3%)Secondary54(56.3%)41(71.9%)95(62.1%)unknown01(1.8%)1(0.7%)No.ofmetastaticsites05(5.2%)1(1.8%)6(3.9%)137(38.5%)13(22.8%)50(32.7%)2+54(56.3%)43(75.4%)97(63.4%)ESR1

m