StGallen 乳腺癌分子分型共识Word格式.docx
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StGallen 乳腺癌分子分型共识Word格式.docx
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membersInternationalBreastCancerStudyGroup,DepartmentofMedicine,EuropeanInstituteofOncology,Milan,Italy;
2DepartmentofSurgery,EmoryUniversitySchoolofMedicine,N.E.Atlanta,USA;
3InternationalBreastCancerStudyGroupandUniversityofSydney,Sydney,Australia;
4InternationalBreastCancerStudyGroupStatisticalCenter,DepartmentofBiostatisticsandComputationalBiology,Dana-FarberCancerInstitute,HarvardMedicalSchool,Boston,USA;
5BreastCenter,KantonsspitalStGallen,StGallen;
6TumorandBreastCenterZeTuP,StGallen,Switzerland
Received21April2011;
accepted23May2011
The12thStGallenInternationalBreastCancerConference(2011)ExpertPaneladoptedanewapproachtotheclassi?
cationofpatientsfortherapeuticpurposesbasedontherecognitionofintrinsicbiologicalsubtypeswithinthebreastcancerspectrum.Forpracticalpurposes,thesesubtypesmaybeapproximatedusingclinicopathologicalratherthangeneexpressionarraycriteria.Ingeneral,systemictherapyrecommendationsfollowthesubtypeclassi?
cation.Thus,‘LuminalA’diseasegenerallyrequiresonlyendocrinetherapy,whichalsoformspartofthetreatmentofthe‘LuminalB’subtype.Chemotherapyisconsideredindicatedformostpatientswith‘LuminalB’,‘HumanEpidermalgrowthfactorReceptor2(HER2)positive’,and‘Triplenegative(ductal)’disease,withtheadditionoftrastuzumabin‘HER2positive’disease.Progresswasalsonotedinde?
ningbettertoleratedlocaltherapiesinselectedcaseswithoutlossofef?
cacy,suchasacceleratedradiationtherapyandtheomissionofaxillarydissectionunderde?
nedcircumstances.Broadtreatmentrecommendationsarepresented,recognizingthatdetailedtreatmentdecisionsneedtoconsiderdiseaseextent,hostfactors,patientpreferences,andsocialandeconomicconstraints.
Keywords:
adjuvanttherapies,earlybreastcancer,StGallenConsensus,subtypes
Introduction
Itisnolongertenabletoconsiderbreastcancerasasingledisease.Subtypescanbede?
nedbygeneticarraytesting[1–3]orapproximationstothisclassi?
cationusingimmunohistochemistry[4–7].Thesesubtypeshavedifferentepidemiologicalriskfactors[8,9],differentnaturalhistories[10–12],anddifferentresponsestosystemicandlocaltherapies[13–17].Thesedifferencesimplythatcliniciansmanagingbreastcancershouldconsidercaseswithinthevariousdistinctsubtypesinordertoproperlyassesstherelevantevidenceandarriveatappropriatetherapeuticadvice.
StGallen2011:
newsandprogress
The12thInternationalBreastCancerConferenceinMarch2011broughttogethersome4300participantsfrom96countriesandaworldwidefacultyrepresentingallrelevantdisciplines.Afterpresentationofrecentresearch?
ndings,a51-memberExpertPanel(seeAppendix1)consideredanumberofquestionsinordertoarriveattreatmentrecommendationsfortheimmediatefuture.AsinpreviousStGallenconferences[18],thePanelwaschargedwithassessingtheevidence,butalsoadvisingonthebasisofexpertopiniononthosequestionswheretheevidencewasambiguousorlacking.Forthe?
rsttime,thisconferenceincludedanexplicitapproachtomanagementofcon?
ictsofinterest(seeAppendix2).
Evidencewaspresentedtosupportalessaggressiveapproachtoaxillarysurgeryinde?
nedcircumstancesandtheuseofmoreconvenientequallyeffectiveapproachestoradiationtherapy.Forsystemictherapy,theemphasisofthisyear’sconsensuswastoreachrecommendationswithineachofthebiologicalsubtypes,sincethesealreadyincorporatemanyoftheriskfactorsandresponsepredictorspreviouslyconsideredseparately.Diseaseextent,hostfactors,patientpreferences,andeconomicandsocialfactorsinevitablyimpactthechoiceanddeliveryofcare.Ingeneral,therecommendationsareintendedtoguidetherapyconsiderationsoutsideclinicaltrialsin?
TheAuthor2011.PublishedbyOxfordUniversityPressonbehalfoftheEuropeanSocietyforMedicalOncology.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNon-CommercialLicense(http:
//creativecommons.org/licenses/by-nc/2.5),whichpermitsunrestrictednon-commercialuse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.specialarticlespecialarticlecommunitieswithreasonablelevelsofavailableresources,butnotingwherepossibletheavailabilityofalternatives,whichmightbeonlymarginallylesseffectivebutlessexpensive.Thisreportwill?
rstreviewthenew?
ndingspresentedatthemeeting(Table1)andthenproceedtosummarizethedeliberationsofthePanel,bringingthesetogethertoformbroadtherapyrecommendations.AnnalsofOncologypaneldeliberationsMorethan100questionswerecirculatedandagreedamongPanelmembersbeforethemeeting.Thesewerepresentedduringthe?
nalsessionoftheconference.Panelmembershadtheopportunitytocomment,andthenvotedelectronicallyeitheryesornooneachquestion,withtheoptiontoabstainiftheyfeltuninformedorcon?
icted.Thedetailedvotesarenotpresentedhere:
Rather,verbaldescriptionsoftheextentofagreementordisagreementaregiveninthefollowingsections.localtherapiesNewresultsfromclinicaltrialssupportedthesafetyofomittingaxillarydissectionnotonlyinpatientswithanegativesentinelnodebiopsy[19]butalsoinpatientswithaclinicallynodenegativeaxillabutpathologicalmacrometastaticinvolvementofoneortwosentinelnodesinthecontextofbreast-conservingsurgerywithtangential?
eldradiationtherapy[20].Thiscontinuesatrendofreducedsurgicalextentwithoutlossofef?
cacy,whichdatesbacktothebreast-conservingapproachespioneeredbyVeronesi[74]andFisher[75].Similarly,recentstudiesinradiationtherapyhavedemonstratedthesafetyandef?
cacyofabbreviatedschedulesforimprovedpatientconvenienceandtheuseofpartialbreastirradiation(PBI)undercertainde?
nedcircumstances.These?
ndingsaresummarizedinTable1.breastcancersubtypesAnalysisofgeneexpressionarrayshasresultedintherecognitionofseveralfundamentallydifferentsubtypesofbreastcancer[1].Becauseitisnotalwaysfeasibletoobtaingeneexpressionarrayinformation,asimpli?
edclassi?
cation,closelyfollowingthatproposedbyCheangetal.[7],hasbeenadoptedasausefulshorthand.Subtypesde?
nedbyclinicopathologicalcriteriaaresimilartobutnotidenticaltointrinsicsubtypesandrepresentaconvenientapproximation.AssummarizedinTable2,thisapproachusesimmunohistochemicalde?
nitionofestrogenandprogesteronereceptor,thedetectionofoverexpressionand/orampli?
cationofthehumanepidermalgrowthfactorreceptor2(HER2)oncogene,andKi-67labelingindex,amarkerofcellproliferation,asthemeansofidentifyingtumorsubtypes.Clearly,thisclinicopathologicalclassi?
cationrequirestheavailabilityofreliablemeasurementsofitsindividualcomponents.Guidelineshavebeenpublishedforestrogenandprogesteronereceptordetermination[76]andforthedetectionofHER2positivity[77].Forclinicaldecisionmaking,thePanelsupportedusingtheUSFoodandDrugAdministrationde?
nitionofHER2positivitybasedontheeligibilitycriteriaforHER2statusdeterminationfromthepivotalclinicaltrials[80,81].Itwasnotedthatclari?
cationstotheASCO/CAPguidelineswereinpreparation,andthesehavesubsequentlybeenpublished[82].Ki-67labelingindexpresentsmoresubstantialchallenges,butimportantguidelinesforthistestareunderdevelopment[7,83–85].Intheproposedclassi?
cation,Ki-67labelingindexischie?
yimportantinthedistinctionbetween‘LuminalA’and‘LuminalB(HER2negative)’subtypes.IfreliableKi-67labelingindexassessmentisnotavailable,somealternativemeasureofproliferationsuchasahistologicalgrademaybeusedinmakingthisdistinction.axillarysurgeryThePanelwasclearlyoftheviewthattheroutineuseofimmunohistochemistrytolookforlow-volumemetastaticdiseaseinsentinelnodeswasnotindicated,sincemetastasesshownonlybyimmunohistochemistrywouldnotaltermanagement.Furthermore,isolatedtumorcells,andevenmetastasesupto2mm(micrometastases)inasinglesentinelnode,werenotconsideredtoconstituteanindicationforaxillarydissectionregardlessofthetypeofbreastsurgerycarriedout.ThePanelacceptedtheoptionofomittingaxillarydissectionformacrometastasesinthecontextoflumpectomyandradiationtherapyforpatientswithclinicallynodenegativediseaseand1–2positivesentinellymphnodesasreportedfromACOSOGtrialZ0011withamedianfollow-upof6.3years[20].ThePanel,however,wasveryclearthatthispractice,basedonaspeci?
cclinicaltrialsetting,shouldnotbeextendedmoregenerally,suchastopatientsundergoingmastectomy,thosewhowillnotreceivewhole-breasttangential?
eldradiationtherapy,thosewithinvolvementofmorethantwosentinelnodes,andpatientsreceivingneoadjuvanttherapy.radiationtherapyThePanelconsideredacceleratedwhole-breastradiotherapytobeanacceptableoptioninselectpatients:
Inparticular,thePanelwasdividedabouttheuseofthisapproachinthepresenceofextensivevascularinvasion.Partialbreastirradiation(PBI)asde?
nitivetreatmentinselectedpatientswassupportedbyalmosthalfofthePanelandbyastrongmajorityforpatientsabovetheageof70.Therewasconsiderableuncertaintyaboutitsuseinlymp
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