王晓稼(英文)：早期接受过人工智能治疗的癌症患者强化治疗的新证据

TheNovelEvidenceforIntensiveTherapyofEarlyBreastCancerPatientsWhoHaveReceivedAI-basedTherapyBeforeZhejiang

CancerHospitalXiaojiaWangAssistanttothepresidentandthechiefofDepartmentofscienceandeducationofZhejiangCancerHospital、DirectorofDepartmentofbreastmedicaloncology；VicepresidentofQuzhouKechengdistritPeople’sHospital.ASCOmember,CSCOexecutivemember.CSCBmemberofstandingcommittee,vicedirectorofZhejiangsocietyforCellbiology/ChairmanofsocietyforClinicalCellBiology.MemberofChinaanti-cancerassociationbreastcancerandanti-cancerdrugcommittee.DirectofZhejianganti-cancerassociation,memberofstandingcommitteeofmedicaloncology,vicememberofstandingcommitteeofbreastcancer.VicechairmanofZhejiangImmunologyassociationandchairmanofTumorImmunologyandBiologicalTreatmentassociation.Presidentofprecisionmedicinecommitteeoftranslationalmedicineassociation.ManagingdirectorofZhejiangAssociationMedicineRehabilitation/ChairmanofTumorassociationMedicineRehabilitation

VicepresidentofZhejiangcancerchemotherapyandbiologicaltherapyassociation.XiaoJiaWangDoctorinOncologyProfessor/Chiefphysician、DoctoralsupervisorUltimateAimofEarlyBreastCancerTherapy

to

reducerecurrence&increasecureIt’sincurableonceearlybreastcanceraccessedtoadvanced,andthesurvivalwaslimitedStudyshowedthatonly20%advancedbreastcancersurvivedfor5yearsTheaimofadjuvanttherapywastoremovemicrometastasisandincreasethechanceofcure40241356720406080100StageI

StageIIStageIII

StageIV

Un-stagedOveralRate

(%)Survival(year)1.KwongA,etal.AnnSurgOncol2011;18:3072-3078.2.ChlebowskiR,etal.Breast2009;18(s2):s1-s11.3.CardosoF,etal.AnnOncol2012;23(Suppl7):vii11-vii19.4.YeoB,etal.BMJ2014;348:g3608.ER+earlybreastcancershavetwopeaksofrecurrenceaftersurgery05101520250.51.52.53.54.55.56.57.58.59.510.5Time

(year)RecurrencerateTotalPositiveLN0PositiveLN1-3PositiveLN≥4Tumordiameter(<1cm)Tumordiameter(1.1-3cm)Tumordiameter(>3cm)ER

positiveERnegativePremenopausePostmenopauseSaphnerT,etal.JClinOncol1996;14:2738-2746.ATLASsupporttheeffectsfor10yearsTAMtherapyversus5yearstherapyHRpositiveBreastcancerpatientsfinished5yearTAMtherapy(N=6846)Continuing5yearadjuvantTAMtherapyStoppingTAMtherapyR10

yearsgroup5yearsgroupPrimaryEndpoints：OSATLAS－AdjuvantTherapyofHRPositiveBreastCancer，

10

years

vs.5

years：Results－RecurrenceandDeathDavisC,etal.2012SABCSAbstractS1-2.ATLAS=AdjuvantTamoxifen-LongerAgainstShorter50403020%±SE10005101550403020%±SE100051015time

(year)time

(year)5years：15years－25.1%10years：15years－21.4%5-9years：RR=0.90(0.79-1.02)10+years：RR=0.75(0.62-0.90)5years：15years－15.0%10years：15

years－12.2%5-9

years：RR=0.97(0.79-1.18)10+

years：RR=0.71(0.58-0.88)DeathRecurrenceReinforcementStrategyforAdjuvantEndocrineTherapyofPremenopauseBCsRecurrentrisk,therapybenefitandadverseeventscomparisonLowriskpatients：onlyTAMtherapyfor5-10

yearsYoungandHighRiskpatients：FirstChoiceofOFS+AI，OFS+TAMcanalsochooseThebesttherapytimeofOFS：5

yearsNotallthepremenopauseBCsneedchemotherapyLong-termfollowup：OFS+Compliance、AdverseEventsandSurvivalBenefitAIreplacingTAMservedasagoldenstandardforendocrinetherapyofpost-menopauseearlyHRpositiveBCsBothinitialtherapyandextendingtherapyfollowing2-3yearsTAM,AIsignificantlyreducedtherecurrencerate.AI

hasbecometotheimportpartofmultiglobalguidelinesforendocrinetherapyHR+TAMAILog-rank2P<0.00001010200589.6%15.3%12.6%19.2%20100036yearHR+Recurrencerate

(%)TAMAI3

yearsrecurrence

3.1%6

yeasrecurrence

3.5%16.1%8.1%5.0%12.6%Log-rank2P<0.00001year5

yearsrecurrence

2.9%8yearsrecurrence

3.9%InitialtherapyExtendingtherapyIngelJ,etal.Presentedat31thSABCS2008.Recurrencerate

(%)ASCO/NCCNguidelinesrecommendtoprolongendocrinetherapytime

But：Howisitafter5yearsAItherapy?Forpost-menopauseHRPositiveBCs，recommed1、TAM10yearstherapy；2、Another5yearsAItherapyfollowing5yearsTAM

therapy；3、Continuing5yearsAItherapyto7-8years

following2-3yearsTAMtherapy；4、5yearsAItherapy（Whetherintensivetherapyis

controversial）；(1)AmericanSocietyofClinicalOncologyEndorsementoftheCancerCareOntarioPracticeGuidelineonAdjuvantOvarianAblationintheTreatmentofPremenopausalWomenWithEarly-StageInvasiveBreastCancer.2014(2)NCCNGuidelines.2015.V1MA.17trail：StudyDesignPrimaryendpoints：DFSSecondaryendpoints：OS/Safety/QOL

Sub-studies：BMD/Bonemarkers,lipidprofileRandomizationaTamoxifenplacebo

qdbletrozole

2.5mgqdaRecent5yearadjuvanttherapy5

yearfollowingtherapy0-3

个月n=2575n=2582 Gossetal.NEnglJMed.2003;349:1793;Gossetal.JNatlCancerInst.2005;97:1262.PostmenopausalER+and/orPgR+AnystatusoflymphglandsECOGPS：0-2Disease-freeandrandomizationan=2575(effort),2154(safety);bn=2582(effort),2145(safety)Breastcancers(N=5157)LNspositiveHR0.61*(95%CI,0.45-0.84)HR0.53*(95%CI,0.36-0.78)HR0.61*(95%CI,0.38-0.98)AllthepatientsDFS*HR0.58;P<0.001DistantDFS*HR0.60;P<0.002OSHR0.82;P=0.3LNsnegativeHR0.45*(95%CI,0.27-0.75)HR0.63(95%CI,0.31-1.27)HR1.52(95%CI,0.76-3.06)MA17trail：ITTanalysisfor30months

.UpdateofGossetal.JClinOncol.2004;22(suppl):847.

Gossetal.JNatlCancerInst.2005;97:1262.Dodwell.CancerTreatmentReviews(2008)34,137–144OS：LymphnodesnegativedidnotimproveOSbenefit,becauseofthefavorableprognosisandlessdeathinthesepatients*ClinicalbenefitsofLetrozolehasstatisticalsignificanceLongtermcharacteristicofLNsandERpositiveBreastCancers？CharacteristicofER(+)BCsrecurrenceafter5yearsadjuvantAItherapyAnnualhazardrates

(%)4.03.02.01.00.04.03.02.01.00.00123456789Follow-uptime(years)Tamoxifen(T)Anastrozole(A)TheATACTrialists’Group.LancetOncol2008;9:45-53TransATAC：

BCIHigh/InterpredictedmorebenefitsforAIverseTAM02468100102030Patients(%)HighH/ILowH/IAITAMTime(year)SgroiD,etal.2012SABCSAbstractS1-9.HR(95%CI)AIvs.TAMH/Ilow1.33(0.65-2.71),P=0.4H/Ihigh0.51(0.27-0.97),P=0.042016

ASCO

ResearchResultsHelpstoChangeTheGuidelinesLong-TermRecurrenceRisksAfterUseofEndocrineTherapyforOnly5Years:RelevanceofBreastTumorCharacteristics(a505)ExtendingadjuvantLetrozolefor5yearsaftercompletinganinitial5yearsAromatizedInhibitortherapyaloneorprecededbyTamoxifeninPostmenopausalWomenwithEarly-StageBreastCancer:ARandomizedPhaseIIIOpenLabelTrial（LBA1）Long-TermRecurrenceRisksAfterUseofEndocrineTherapyforOnly5Years:RelevanceofBreastTumorCharacteristics(a505)HongchaoPan,etal.2016ASCOAbstracta505.ER+BCs：Endocrinetherapyduration5yearsofadjuvantendocrinetherapy(ET)substantiallyreduceslong–termrecurrencerisk*ContinuingETpastyear5yieldsanadditionalriskreduction,butadditionalside-effects*TohelpdecidewhoshouldcontinueET,weneedtoknowtheprognosisifnofurtherETisgiven*References：EBCTCG（tamoxifen）Lancet2011；378:771，EBCTCG（AI）Lancet2015;386:1341,MA.17(AI)NEJM2003;349:1793,ASCO2016Abs.LBA1,ATLASLancet2013;381:805,aTTomJCO2013;31;18(supp5)HongchaoPan,etal.2016ASCOAbstract505.Methods：StudyofprognosticfactorsDatafrom91trialsoneachindividualwithER+diseaseallocatedonly5yearsofET*Analysejustthe46,000women(n=46K)whowerestillaliveanddisease-freeatyear5*ETwas¾TAMand¼AI(orpartlyAI);analysesareonlyofT1orT2tumours(diameter≤20or21-50mm)with＜10nodes(N0-N9)&age＜80after5

yearsETHongchaoPan,etal.2016ASCOAbstract505.EndpointsAnybreastcancerevent(distant,localorcontralateral),ignoringunrelateddeathsDistantrecurrence(asdefinedbyeachtrial),ignoringlocalorcontralateraleventsAnalyses：Coxregressions（adjustedT、Nstage）andKaplan-Meier

graphs（%

riskand95%CI，withthedistantrecurrencerateinyears15-20takenastheratefromyears10-20,ie,no.ofevents/person-years）HongchaoPan,etal.2016ASCOAbstract505.Mainfindings：Long-termrisksEvenafter5yearsofET,recurrencescontinuesteadily,atleasttoyear20Absoluterecurrenceriskinyears5-20isappreciable,evenforT1N0diseaseHongchaoPan,etal.2016ASCOAbstract505.Analyses：Coxregressions（adjustedT、Nstage）andKaplan-Meier

graphs（%

riskand95%CI，withthedistantrecurrencerateinyears15-20takenastheratefromyears10-20,ie,no.ofevents/person-years）Lowest-stage(T1N0)disease:RiskofANYbreastcancerevent

21%risk,years5-20(14%DISTANTrecurrence+7%onlylocalorcontrralateral)HongchaoPan,etal.2016ASCOAbstract505.HongchaoPan,etal.2016ASCOAbstract505.Lowest-stage(T1N0)disease:RiskofDISTANTrecurrence

14%riskinyears5-20(ie,about1%peryear)Node-negative(N0)disease:EffectoftumorsizeHongchaoPan,etal.2016ASCOAbstract505.Smalltumours(T1disease):EffectofnodalstatusHongchaoPan,etal.2016ASCOAbstract505.HongchaoPan,etal.2016ASCOAbstract505.Largertumours(T2disease):EffectofnodalstatusLowest-stage(T1N0)disease:EffectoftumourgradeHongchaoPan,etal.2016ASCOAbstract505.Summary：Need20-yearperspectiveonER+diseaseIfETtherapyalonefor5years,distantrecurrence5-20yearscontinuesteadily：Every5yearsrecurrenceratesforT1N0

patientsare1.4%、1.7%

and1.8%,respectively；distantmetastasisratesare0.8%,1.0%

and1.2%,respectively。WithoutfurtherET,distantrecurrenceriskinyears5-20is~14%forT1N0，andmuchgreaterforT2N0orN+diseaseHongchaoPan,etal.2016ASCOAbstract505.ExtendingadjuvantLetrozolefor5yearsaftercompletinganinitial5yearsAromatizedInhibitortherapyaloneorprecededbyTamoxifeninPostmenopausalWomenwithEarly-StageBreastCancer:ARandomizedPhaseIIIOpenLabelTrial（LBA1）LBA1_MA.17R

StudyDesignScreenedMA.17randomizedMA.17RrandomizedMA.17R随机入组5yrsofletrozole5yrsofplacebo5yrsofletrozole5yrsofplacebo5yearsofTAM5yearsofAI5yrsofletrozolePrimaryendpoint：DFSSecondaryendpoints：OS、ContralateralBreastCancer、Safety、QualityofLife（QOL）、