大四下乳腺多學(xué)科治療選修課

乳腺癌的治療

從外科走向多學(xué)科沈坤煒上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院乳腺疾病診治中心BreastCancerisChangingFace2007TrendsofIncidencebyAgein5-yearIntervalPeriods,1973-2007inShanghaiTwopeaksbegantomergeintooneAgeneralelevationamong45-80LocalRecurrenceRatesColumbiaClinicalClassification

FIVEGRAVESIGNSEdemaofskin(<1/3)SkinulcerationFixationoftumortochestwallMassiveaxillarylymphnodeinvolvement(2.5cm)Fixationofaxillarynodes1915-1942HaagensenInoperableBreastCancerTwoormoregravesignsExtensiveedemaofskin(>1/3)SatelliteskinnodulesInflammatorycarcinomaSupraclavicularlymphnodesInternalmammary/parasternaltumorEdemaofarmDistantmatastasesMultidisciplinaryManagementofBreastCancerUmbertoVeronesiHeadoftheNationalCancerInstituteinMilanThedirectoroftheEuropeanInstituteofOncology

ComparingRadicalMastectomywithQuadrantectomy,-AxillaryDissection,andRadiotherapyinPatientswithSmallCancersoftheBreastNewEnglandJournalofMedicine1981;305:6-11701patientsCALN(—)T≤2cm(1973-1980)Halstedmastectomy(349pts)Q.+ALND+RT(352pts)Result:NSin7.5yearssurvivalrateNSABPB-061976-1984N=1,851MultidisciplinaryManagementofBreastCancerBreastReconstructionMultidisciplinaryManagementofBreastCancerLymphaticMappingandSentinelNodeBiopsyThe“sentinel”nodeisthefirstnodetoreceivelymphaticdrainagefromaprimarytumor.Thus,itisthefirstnodetowhichatumorwillmetastasize.Ifthesentinelnodeisnegativeformetastaticdisease,theremainingnodesinthelymphaticbasinarealsolikelytobenegative.SentinelLymphNodeBiopsyMultidisciplinaryManagementofBreastCancerBonadonna:CMFTrial Total Failures

ControlGroup 179 43 CMF 207 1 p=0.00002GBonadonnaetal.NEJM1976,updated:NEJM19951970’sCMF1980’sAC1990’sACT2000’sACTdd2000’sTAC2009TACvTCvTCB

EBCTCGMeta-Analysis2005-06

BreastCancerMortalityPetoRonbehalfoftheEarlyBreastCancerTrialists’CollaborativeGroup(EBCTCG).PresentedatSABCS2007,December13,2007.SanAntonio,TX.Deathrates(%/year:total–rateinwomenwithoutrecurrence)&logrankanalysesTaxanes>Anthra.>CMF>NoChemo.MultidisciplinaryManagementofBreastCancerSurrogateDefinitionsOfIntrinsicSubtypesOfBreastCancer2011ER,PR,HER,andKi67Surrogatedefinitionsofintrinsicsubtypes2013IntrinsicsubtypeClinico-pathologicsurrogatedefinitionNotesLuminalAER&PRposHER2negKi-67lowRecurrencerisklow*AlevelofKi-67<14%bestcorrelatedwiththegene-expressiondefinitionofLuminalA.PRcut-pointof≥20%bestcorrespondtoLuminalAsubtype.LuminalBHER2neg:ERposHER2negOneof:Ki-67high/PRnegorlow/Recurrenceriskhigh*HER2pos:ERposHER2

posEitherahighKi-67valueoralowPRvaluemaybeusedtodistinguishbetween‘LuminalA-like’and‘LuminalB-like(HER2negative)’.Erb-B2overexpressionHER2posER&PRnegBasal-likeER&PRnegHER2neg80%overlapbetween‘TN’andintrinsic‘basal-like’subtype.‘TN’alsoincludessomespecialhistologicaltypessuchasadenoidcysticcarcinoma.SystemicTreatmentmendationsforSubtypesSystemictreatmentmendations2013SubtypeTypeoftherapyNotesontherapyLuminalAET:mostcriticalandoftenusedaloneRelativeindicationsforcytotoxics(amajority)(i)high21-geneRS(i.e.>25);(ii)70-genehighriskstatus;(iii)grade3;(iv)≥4LN(aminorityrequiredonlyonenode).LuminalB(HER2neg)ETforall,CTformostLuminalB(HER2pos)CT+anti-HER2+ETNodataareavailabletosupporttheomissionofcytotoxicsinthisgroup.HER2pos(non-luminal)CT+anti-HER2Thresholdforuseofanti-HER2therapywasdefinedaspT1borlargertumourornode-positivity.Triplenegative(ductal)CT‘Specialhistologicaltypes’A.EndoresponsiveB.Endonon-responsiveETCTAdenoidcysticcarcinomasmaynotrequireanyadjuvantcytotoxics(ifnodenegative).MultidisciplinaryManagementofBreastCancerBreastCancerDiseases–201…AllBreastCancersER+65-75%HER2+15-20%Triplenegative15%HER3+IGFR1+p95+4%P53mut30-40%FGFR1Ampl8%PTENloss30-50%PI3Kmut10%BRCAMut8%BiochimicaetBiophysicaActa1795(2009)62–81

ERsignalingpathwayEstrogensignalingpathwayOsborneCK,SchiffR.Annu.Rev.Med.201162:233-47.geneamplification

overexpression

ofHER2protein

(10-foldto100-fold)NORMALCELLTUMORCELLHER2geneHER2proteinHerceptin

monoclonalantibody

selectivelytargets

theextracellular

domainofthe

HER2proteinNUCLEOLUSCELLSURFACEWITHEXTRACELLULARDOMAINS

OFHER2PROTEINHER2HER2HER2HER2HER2HER2HER2HER2Herceptin?MechanismofActionConstitutiveactivationofdownstreamsignalingpathways5-yrTAMvs.NotinER+BreastCancerEBCTCG,Lancet,2005:1687-717TrastuzumabintheTreatmentofBreastCancerGabrielN.Hortobagyi,M.D.Theresultsaresimplystunning.Clearly,theresultsreportedinthisissueofthejournalarenotevolutionarybutrevolutionary.Trastuzumabandthetworeportsinthisissuewillcompletelyalterourapproachtothetreatmentofbreastcancer.Editorial,Oct20,2005EarlyDetectionTrendsinincidenceofbreastcancerinselectedcountriesTrendsinmortalityfrombreastcancerinselectedcountriesFerlayJ,etal.IntJCancer2010TrendsinMortalityandIncidencefromBreastCancerMultidisciplinaryManagementofBreastCancerMultidisciplinaryManagementofBreastCancerBreastCancerMultidisciplinaryManagement:MultidisciplinaryClinicMultidisciplinaryConference——thestandardcareofbreastcancer.MultidisciplinaryManagementofBreastCancerComprehensiveBreastHealthCenter

ShanghaiRuijinHospital

門診日間化療“一站式”服務(wù)病房MultidisciplinaryConferenceMultidisciplinaryConferenceGoal:TreatmentIndividualization!Movingawayfromonesizefitsall!PersonalizedRxforBreastCancer:Hope/Hype?EdithA.Perez,M.D.DeputyDirector,MayoClinicComprehensiveCancerCenterGroupViceChair,Alliancefor

ClinicalTrialsinOncologySereneM.andFrancesC.DurlingProfessorofMedicineMayoClinic

Jacksonville,FloridaPersonalizedRxforBreastCancerHype–yesHope–YES!THANKYOU“Conventional”WisdomofYesterday…BreastcancerisonediseaseOne-size-fits-alltreatmentapproachBystage,nodalstatus,andhormonereceptorstatus“ConventionalWisdom”ofToday…Breastcancerisaheterogeneousdiseasecomprisedofdifferentmolecularsubtypesbasedongene/proteinexpressionprofilingOutlineGenerallandscapeofclinicalresearchinbreastcancerProspectivebiomarkervalidation:AfielddrivenbylargeconsortiumandtrialsAdjuvanttrialsEarlydrugdevelopment:newdesignsCohorts:Anemergingresearchtoolinbreastcancerarea?TAILORxTrialMINDACTTrialRxPondersTrialIndividualizedTherapyDecisionSupportSystemClinicallyandMolecularlyAppropriateTherapyMultidisciplinaryGenomicsRoundsMoussesConfidentialMolecularPathwayKnowledgeMining

InformedConsentonUSONIRB-approvedprotocolN=1CLIACLIAvalidationIdentifyingTherapeuticTargetsonWGSofmTNBCCancerIntegratedAnalysisTumorDNA/RNAandgermlineDNALifeSOLiD4O’ShaugnessyetalProcSA2011Mole