Overview of the Treatment of Newly Diagnosed, Non-metastatic Breast Cancer

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OfficialreprintfromUpToDate www.uptodate.com2015UpToDate

AuthorsAlphonseTaghian,MD,PhDMoatazNElGhamry,MDSofiaDMerajver,MD,PhD

SectionEditorDanielFHayes,MD

DeputyEditorDonSDizon,MD,FACP

Overviewofthetreatmentofnewlydiagnosed,nonmetastaticbreastcancer

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Apr2015.|Thistopiclastupdated:Aug25,2014.

INTRODUCTIONGlobally,breastcanceristhemostfrequentlydiagnosedcancerandtheleadingcauseofcancerdeathinwomen.IntheUnitedStates,breastcanceristhemostcommonlydiagnosedcancerandthesecondmostcommoncauseofcancerdeathinwomen.Inaddition,breastcanceristheleadingcauseofdeathinwomenages40to49years.

Breastcanceristreatedwithamultidisciplinaryapproachinvolvingsurgicaloncology,radiationoncology,andmedicaloncology,whichhasbeenassociatedwithareductioninbreastcancermortality[1].

Thistopicwillprovideanoverviewoftheinitialtreatmentofbreastcancerandposttreatmentsurveillance.Theepidemiology,clinicalmanifestations,diagnosis,stagingofbreastcancer,andspecificdiscussionsofthemultimodalitytreatmentsforearlybreastcancerandtheapproachtometastaticdiseasearediscussedelsewhere.(See"Clinicalfeatures,diagnosis,andstagingofnewlydiagnosedbreastcancer"and"Systemictreatmentformetastaticbreastcancer:Generalprinciples"and"Metastaticbreastcancer:Localtreatment".)

Becauseductalcarcinomainsitu(DCIS)andinvasivebreastcanceraremanageddifferently,wewillrestrictdiscussioninthistopictoinvasivebreastcancer.AdiscussiononDCISiscoveredseparately.(See"Breastductalcarcinomainsitu:Epidemiology,clinicalmanifestations,anddiagnosis"and"Ductalcarcinomainsitu:Treatmentandprognosis".)

PATIENTSTRATIFICATIONThevastmajorityofpatientswithnewlydiagnosedbreastcancerintheUnitedStatesanddevelopedcountrieshavenoevidenceofmetastaticdisease.Forthesepatients,thetreatmentapproachdependsonthestageatpresentation.Fortreatmentpurposes,breastcancerischaracterizedusingtheTumor,Node,Metastasessystem(TNM)(table1):

Approximately5percentofpatientswillhavesimultaneousmetastaticdiseaseidentifiedattheinitialpresentation(denovostageIVbreastcancer).Thetreatmentapproachtothesepatientsisdiscussedseparately.(See"RoleofbreastsurgeryforstageIVbreastcancer"and"Systemictreatmentformetastaticbreastcancer:Generalprinciples".)

EARLYSTAGEBREASTCANCERIngeneral,patientswithearlystagebreastcancerundergoprimarysurgery(lumpectomyormastectomy)tothebreastandregionalnodeswithorwithoutradiationtherapy(RT).Followingdefinitivelocaltreatment,adjuvantsystemictherapymaybeofferedbasedonprimarytumorcharacteristics,suchastumorsize,grade,numberofinvolvedlymphnodes,thestatusofestrogen(ER)andprogesterone(PR)receptors,andexpressionofthehumanepidermalgrowthfactor2(HER2)receptor.

BreastconservingtherapyBreastconservingtherapy(BCT)iscomprisedofbreastconservingsurgery(BCS,ie,lumpectomy)plusradiationtherapy(RT).ThegoalsofBCTaretoprovidethesurvivalequivalentofmastectomy,acosmeticallyacceptablebreast,andalowrateofrecurrenceinthetreatedbreast.BCTallows

EarlystageThisincludespatientswithclinicalstageI,IIA,orasubsetofstageIIBdisease(T2N1).

LocallyadvancedThisincludesasubsetofpatientswithclinicalstageIIBdisease(T3N0)andpatientswithstageIIIAtoIIICdisease.

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patientswithinvasivebreastcancertopreservetheirbreastwithoutsacrificingoncologicoutcome.SuccessfulBCTrequirescompletesurgicalremovalofthetumor(withnegativesurgicalmargins)followedbymoderatedoseRTtoeradicateanyresidualdisease.(See"Breastconservingtherapy".)

CriteriathatprecludeBCTinclude(see"Breastconservingtherapy",sectionon'PatientselectionforBCT'):

ForpatientswhodesireBCTbutarenotcandidatesatthetimeofpresentation,analternativeapproachistheuseofneoadjuvanttherapy,whichmayallowforBCSwithoutcompromisingsurvivaloutcomes.(See'Neoadjuvantsystemictherapy'below.)

MastectomyAmastectomyisindicatedforpatientswhoarenotcandidatesforBCTandthosewhoprefermastectomy.(See"Mastectomy:Indications,types,andconcurrentaxillarylymphnodemanagement",sectionon'Selectioncriteriaformastectomy'.)

RoleofRTPostmastectomyRTisindicatedforpatientsathighriskforlocalrecurrence,suchasthosewithcancerinvolvingthedeepmarginsandpathologicallyinvolvedaxillarylymphnodes.IfthelikelihoodofpostmastectomyRTishighpreoperatively,thismayaffectthechoiceofmastectomytype,thechoiceofthereconstructiveapproach,andoptimaltimingofthebreastreconstruction(immediateversusdelayed).BasedupontheEarlyBreastCancerTrialistsCollaborativeGroupmetaanalysisof3786womenwithinvasivebreastcancerundergoinganaxillarydissectionandmastectomy,therewasareductioninrecurrencesfornodepositivewomen([n=1314,onetothreenodespositive]and[n=1772,fourormorenodespositive])undergoingpostmastectomyradiation,butnotfornodenegativewomen[2].

Thus,preoperativecoordinationofcareassuresthebestoutcome.Inmanycenters,thisisaccomplishedbymultidisciplinarybreastclinics.(See"Adjuvantradiationtherapyforwomenwithnewlydiagnosed,nonmetastaticbreastcancer",sectionon'Patientstreatedwithmastectomy'.)

EvaluationoftheaxillarynodesTheriskformetastasestotheaxillarynodesisrelatedtotumorsizeandlocation,histologicgrade,andthepresenceoflymphaticinvasionwithintheprimarytumor.Althoughinternalmammaryorsupraclavicularnodesmaybeinvolvedattheinitialpresentation,theyrarelyoccurintheabsenceofaxillarynodeinvolvement.(See"Managementoftheregionallymphnodesinbreastcancer",sectionon'Internalmammarylymphnodes'and"Managementoftheregionallymphnodesinbreastcancer",sectionon'Supraclavicularlymphnodes'.)

Theevaluationoftheregionalnodesdependsonwhetheraxillaryinvolvementissuspectedpriortosurgery:

Forpatientspresentingwithclinicallysuspiciousaxillarylymphnodes,apreoperativeworkupincludingultrasoundplusfineneedleaspiration(FNA)orcorebiopsycanhelptodeterminethebestsurgicalapproach.

MulticentricdiseaseLargetumorsizeinrelationtobreastPresenceofdiffusemalignantappearingcalcificationsonimaging(ie,mammogramormagneticresonanceimaging[MRI])

PriorhistoryofchestRT(eg,mantleradiationforHodgkindisease)PregnancyPersistentlypositivemarginsdespiteattemptsatreexcision

Forpatientswithapositivebiopsy,anaxillarynodedissectionshouldbeperformedatthetimeofbreastsurgery.(See"Techniqueofaxillarylymphnodedissection".)

Forpatientspresentingwithanegativebiopsy,nofurtherworkupisrequiredpriortosurgery.Thesepatientsshouldundergoasentinellymphnodebiopsy(SLNB)atthetimeofsurgery.(See"Diagnosis,stagingandtheroleofsentinellymphnodebiopsyinthenodalevaluationofbreastcancer"and"Sentinellymphnodebiopsyinbreastcancer:Techniques".)

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AdjuvanttherapySystemictherapyreferstothemedicaltreatmentofbreastcancerusingendocrinetherapy,chemotherapy,and/orbiologictherapy.(See"Adjuvantchemotherapyforhormonereceptorpositiveornegative,HER2negativebreastcancer"and"AdjuvantmedicaltherapyforHER2positivebreastcancer"and"Adjuvantendocrinetherapyfornonmetastatic,hormonereceptorpositivebreastcancer".)

Tumorcharacteristicspredictwhichpatientsarelikelytobenefitfromspecifictypesoftherapy.Forexample,hormonereceptorpositivepatientsbenefitfromtheuseofendocrinetherapy.Inaddition,patientswithhumanepidermalgrowthfactorreceptor2(HER2)positivecancersbenefitfromtreatmentusingHER2directedtreatment.(See"Prognosticandpredictivefactorsinearly,nonmetastaticbreastcancer".)

Forpatientswithearlystagebreastcancer,treatmentisbasedontumorcharacteristics,patientstatus,andpatientpreferences:

LOCALLYADVANCEDBREASTCANCERLocallyadvancedbreastcancerisbestmanagedwithmultimodalitytherapyemployingsystemicandlocoregionaltherapy.(See'Patientstratification'above.)

NeoadjuvantsystemictherapyMostpatientswithlocallyadvancedbreastcancershouldreceiveneoadjuvantsystemictherapy.Thegoaloftreatmentistoinduceatumorresponsebeforesurgeryandenablebreast

PatientswithaclinicallynegativeaxillaryexaminationshouldundergoaSLNBatthetimeofsurgery.FurtherevaluationoftheregionalnodesdependsonthefindingsatSLNB.

Patientswhohavelessthanthreepathologicallyinvolvedsentinelnodesmaynotrequireacompleteaxillarynodedissection[3].However,whetherornotpatientswiththreeormorepathologicallyinvolvedsentinelnodesshouldundergoanaxillarynodedissectionisbestdeterminedonanindividualizedbasis,takingintoaccountallothertumorriskfactorsandthepatientsperformancestatusandcomorbidities.(See"Diagnosis,stagingandtheroleofsentinellymphnodebiopsyinthenodalevaluationofbreastcancer".)

Patientswithhormonereceptorpositivebreastcancershouldreceiveendocrinetherapy.Whethertheyalsoshouldreceiveadjuvantchemotherapydependsonpatientandtumorcharacteristics.(See"Adjuvantendocrinetherapyfornonmetastatic,hormonereceptorpositivebreastcancer"and"Adjuvantchemotherapyforhormonereceptorpositiveornegative,HER2negativebreastcancer",sectionon'Indicationsfortreatment'.)

Weofferchemotherapytopatientswithearlystagehormonereceptorpositivecancersthathavehighriskcharacteristics,suchashighgradetumor,largetumorsize(2cm),pathologicallyinvolvedlymphnodes,and/orhigh21generecurrencescore(31).

Intheabsenceofhighriskfeatures,weprefernottoadministerchemotherapy.

ForpatientswithER/PRandHER2negativedisease(triplenegativebreastcancer),weprefertoadministeradjuvantchemotherapyifthetumorsizeis0.5cm.BecausethesepatientsarenotcandidatesforendocrinetherapyortreatmentwithHER2directedagents,chemotherapyistheironlyoptionforadjuvanttreatment,followingorbeforeradiotherapy.Patientswithatriplenegativebreastcancer1cmshouldreceiveacombinationofchemotherapyplusHER2directedtherapy.Themanagementofsmall(1cm)HER2positivebreastcancersiscontroversial.(See"AdjuvantmedicaltherapyforHER2positivebreastcancer",sectionon'Patienteligibility'.)

Followingchemotherapy,patientswithERpositivediseaseshouldalsoreceiveadjuvantendocrinetherapy.(See"AdjuvantmedicaltherapyforHER2positivebreastcancer"and"Adjuvantendocrinetherapyfornonmetastatic,hormonereceptorpositivebreastcancer",sectionon'PatientswithHER2positivetumors'.)

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conservation.

Neoadjuvanttherapyresultsinlongtermdistantdiseasefreesurvivalandoverallsurvival(OS)comparabletothatachievedwithprimarysurgeryfollowedbyadjuvantsystemictherapy.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Patientselection'.)

Ourapproachtotheselectionoftreatmentintheneoadjuvantsettingisoutlinedbelow:

SurgicalapproachafterneoadjuvanttreatmentAllpatientsshouldundergosurgeryfollowingneoadjuvantsystemictherapy,eveniftheyhaveacompleteclinicaland/orradiologicalresponse.Inaddition,patientswhoexperienceprogressionwhileonneoadjuvantsystemictherapyshouldproceedwithsurgery,ratherthanswitchingthechemotherapyregimen.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Definitivesurgicaltreatment'.)

PrimarytumorThechoicebetweenbreastconservationandmastectomyafterneoadjuvanttreatmentisdependentonthetreatmentresponseandpatientcharacteristics(eg,breastsizeinrelationtoresidualtumorsize).Similarcriteriausedinthetreatmentofearlystagebreastcancerareapplied.However,patientswhopresentwithalarge(ie,T4)breastlesionshouldundergoamastectomyfollowingneoadjuvanttreatment.(See'Breastconservingtherapy'aboveand'Mastectomy'above.)

RegionalnodesAllpatientsrequireasurgicalevaluationoftheregionalnodesfollowingneoadjuvanttreatment.(See'Evaluationoftheaxillarynodes'aboveand"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Nodalevaluation'.)

PrimarysurgeryAlthoughsomepatientsmaybecandidatesforprimarysurgeryatpresentation,patientswithlocallyadvanceddiseasehaveanextremelyhighriskoflocalrecurrenceanddistantmetastases[4].Asaresult,weprefertotreatpatientswithlocallyadvancedbreastcancerwithneoadjuvantsystemictherapyfirst.

Forpatientswhoproceedwithprimarysurgery,basedonpathologicalresults,postoperativeradiationtherapy(RT)andadjuvanttreatmentshouldbeadministered.(See"Radiationtherapytechniquesfornewlydiagnosed,nonmetastaticbreastcancer"and'Adjuvanttherapy'below.)

AdjuvanttherapyTheuseofpostoperative(adjuvant)systemictherapyisguidedbythepatientsclinicalstatusandtumorcharacteristics:

Formostpatientswithhormonereceptorpositivedisease,werecommendchemotherapyintheneoadjuvantsettingratherthanendocrinetherapy.Chemotherapyisassociatedwithhigherresponseratesinashortertimeperiod.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Patientselection'.)

Forpatientswithhumanepidermalgrowthfactorreceptor2(HER2)positivebreastcancer,aHER2directedagent(eg,trastuzumabwithorwithoutpertuzumab)shouldbeaddedtothechemotherapyregimen.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'HER2directedtherapy'.)

Werestrictendocrinetherapyintheneoadjuvantsettingtothetreatmentofpostmenopausalpatientswithhormonereceptorpositivediseasewhoarenotsurgicalcandidates(regardlessoftumorsize)witharelativeorabsolutecontraindicationtochemotherapy(ie,significantmedicalcomorbidities,advancedage,orpoorperformancestatus).(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Endocrinetherapy'and"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Patientselection'.)

Patientswhodidnotreceiveneoadjuvantsystemictherapyshouldreceiveadjuvanttreatment.Theuseofchemotherapy,biologictherapy,and/orendocrinetherapyisguidedbythesameprinciplesusedtodeterminetreatmentforearlystagebreastcancer.(See'Adjuvanttherapy'above.)

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Patientstreatedwithneoadjuvantendocrinetherapywhoundergosurgeryshouldcontinueendocrinetherapyintheadjuvantsetting.Whetherornottoadministeradjuvantchemotherapyshouldbeindividualized.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Objectives'.)

SPECIALCONSIDERATIONS

FertilitypreservationCliniciansshoulddiscusswithpatientstheriskofinfertilityandpossibleinterventionstopreservefertilitypriortoinitiatingpotentiallygonadotoxictherapy.Thisdiscussionshouldoccursoonafterdiagnosis,sincesomeinterventionstopreservefertilitytaketimeandcoulddelaythestartoftreatment.ThisisconsistentwithguidancefromtheAmericanSocietyofClinicalOncology[5].Thetopicoffertilitypreservationiscoveredindetailseparately.(See"Fertilitypreservationinpatientsundergoinggonadotoxictreatmentorgonadalresection".)

OlderwomenForsomepatientswithestrogenreceptor(ER)positivebreastcancer,inwhomsurgeryisnotanoptionorlifeexpectancyislimited,primaryhormonaltreatmentwitheithertamoxifenoranaromataseinhibitorwithoutsurgeryorradiationtherapy(RT)canbeused[6].Weprefertoindividualizetreatmentbasedonthepresenceofmedicalcomorbiditiesandpatientandclinicianpreference.(See"Generalprinciplesonthetreatmentofearlystageandlocallyadvancedbreastcancerinolderwomen",sectionon'Surgeryversusprimaryendocrinetherapyinwomenwithhormonereceptorpositivedisease'.)

MalebreastcancerThetopicofmalebreastcancerisdiscussedseparately.(See"Breastcancerinmen".)

BreastcancerinpregnancyThetreatmentofbreastcancerinpregnancyisdiscussedseparately.(See"Gestationalbreastcancer:Treatment".)

PROGNOSISThemajorityofbreastcancerrecurrencesoccurwithinthefirstfiveyearsofdiagnosis,particularlywithhormonereceptornegativedisease.However,somerecurrencesoccurmuchlater.InonestudyofpatientswithstageI,II,orIIIbreastcancerwhowerewithoutevidenceofdiseasefiveyearsoutfromtheoriginaldiagnosis,therecurrencerisksinthesubsequentfiveandtenyearswerestill11and19percent,respectively[7].(See"Patternsofrelapseandlongtermcomplicationsoftherapyinbreastcancersurvivors",sectionon'Relapse

Forpatientswhoreceivedthefullcourseofplannedneoadjuvantchemotherapy(see"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Chemotherapy'):

Patientswithhormonereceptorpositivebreastcancershouldreceiveendocrinetherapytoreducetheriskofbreastcancerrecurrenceandbreastcancerrelatedmortality.ThereisnoevidencethattheadditionoffurtherchemotherapyintheformofadjuvanttreatmentimprovesOS.Theselectionofendocrinetherapyismadeaccordingtomenopausalstatus.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Endocrinetherapy'.)

Patientswithhormonereceptornegativebreastcancerwouldtypicallynotreceivefurtherchemotherapyintheadjuvantsetting,asthereisnoevidencethattheadditionofadjuvantchemotherapyimprovesOS.Thesepatientsshouldbeginposttreatmentsurveillance.(See"Approachtothepatientfollowingtreatmentforbreastcancer",sectionon'Guidelinesforposttreatmentfollowup'.)

Insomeexceptionalcaseswherethetumorprogressedduringneoadjuvanttherapyorifthecompleteneoadjuvanttherapycouldnotbedeliveredatthenormallevelsofintensity,adjuvantchemotherapyshouldbediscussedandconsidered.

PatientswithHER2positivebreastcancershouldreceiveoneyearoftrastuzumabfollowingcompletionofsurgerywithouttheadditionoffurtherchemotherapy.ThisrecommendationisbasedonstudiesofadjuvantchemotherapywithorwithouttrastuzumabthatdemonstratedthattheadditionofoneyearoftrastuzumabsignificantlyimprovesdiseasefreesurvivalandOS.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'HER2directedtreatment'.)

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patterns'.)

Patientswithearlystagebreastcancerhaveabetterprognosisthanthosepatientsdiagnosedwithlocallyadvanceddisease.AccordingtoTumor,Nodes,Metastases(TNM)stage,fiveyearrelativesurvivalratesbystageforpatientspresentingwithstageI,IIA,IIB,IIIA,IIIB,andIVdiseasewere95,85,70,52,48,and18percent,respectively[8].Bothyounger(age

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SUMMARY

PatientstratificationPatientswithanewdiagnosisofbreastcancercanbestratifiedbytheirextentofdisease(see'Patientstratification'above):

Earlystagebreastcancer

PatientswithclinicalstageI,IIA,orasubsetofstageIIBdisease(T2N1)areclassifiedashavingearlystagebreastcancer.

PatientswithaT3tumorwithoutnodalinvolvement(T3N0,asubsetofpatientswithclinicalstageIIBdisease)andthosewhopresentwithstageIIIAtoIIICdiseaseareclassifiedashavinglocallyadvancedbreastcancer.

Approximately5percentofpatientswillpresentwithdistantmetastases(stageIV)atdiagnosis.

Thesurgicalapproachtotheprimarytumordependsonthesizeofthetumor,whetherornotmultifocaldiseaseispresent,andthesizeofthebreast.Theoptionsincludebreastconservingtherapy(breastconservingsurgeryplusradiationtherapy[RT])ormastectomy(withorwithoutRT).Bothapproachesresultinequivalentcancerspecificoutcomes.(See'Earlystagebreastcancer'aboveand"Breastconservingtherapy"and"Mastectomy:Indications,types,andconcurrentaxillarylymphnodemanagement".)

Theriskformetastaticdiseaseintheregionalnodesisrelatedtotumorsize,histologicgrade,andthepresenceoflymphaticinvasionwithintheprimarytumor.Althoughinternalmammaryorsupraclavicularnodesmayalsobeinvolvedattheinitialpresentation,theyrarelyoccurintheabsenceofaxillarynodeinvolvement.Thesurgicalapproachtotheregionalnodesdependsontheclinicalstatusoftheaxilla(see'Evaluationoftheaxillarynodes'above):

Forpatientspresentingwithclinicallysuspiciousaxillarynodes,apreoperativeworkupincludingultrasoundpluslymphnodebiopsycanhelptodeterminethebestsurgicalapproach.Ifthelymphnodebiopsyispositive,anaxillarynodedissectionshouldbeperformed.Ifthelymphnodebiopsyisnegative,asentinellymphnodebiopsy(SLNB)atthetimeofsurgeryshouldbeperformed.(See"Managementoftheregionallymphnodesinbreastcancer",sectionon'Axillaryultrasound'and"Managementoftheregionallymphnodesinbreastcancer",sectionon'Axillarydissection'and"Managementoftheregionallymphnodesinbreastcancer",sectionon'Sentinellymphnodebiopsy'.)

Patientswhopresentwithaclinicallynegativeaxilladonotrequireapreoperativeworkup.ThesepatientsshouldundergoanSLNBatthetimeofdefinitivebreastsurgery.Patientswhohave

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Locallyadvancedbreastcancer

adjuvantchemotherapyifthetumorsizeis>0.5cm.(See"Epidemiology,riskfactorsandtheclinicalapproachtoER/PRnegative,HER2negative(Triplenegative)breastcancer"and"Adjuvantchemotherapyforhormonereceptorpositiveornegative,HER2negativebreastcancer".)

PatientswithHER2positivebreastcancer>1cminsizeshouldreceiveacombinationofchemotherapyplusHER2directedtherapy.Followingchemotherapy,patientswithERpositivediseaseshouldalsoreceiveadjuvantendocrinetherapy.(See"AdjuvantmedicaltherapyforHER2positivebreastcancer"and"Adjuvantendocrinetherapyfornonmetastatic,hormonereceptorpositivebreastcancer",sectionon'PatientswithHER2positivetumors'.)

Mostpatientswithlocallyadvanced,inoperablebreastcancershouldreceiveneoadjuvantsystemictherapyratherthanproceedingwithprimarysurgery.Thesepatientsareusuallynotcandidatesforbreastconservationattheirinitialpresentation.Neoadjuvanttreatmentimprovestherateofbreastconservationwithoutcompromisingsurvivaloutcomes.(See'Neoadjuvantsystemictherapy'above.)

Formostpatients,werecommendchemotherapyintheneoadjuvantsettingratherthanendocrinetherapy.Chemotherapyisassociatedwithhigherresponseratesinafastertimeframe.AHER2directedagent(ie,trastuzumab)shouldbeaddedtothechemotherapyregimenfortumorsthatareHER2positive.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Eligibilityforprimarysurgery'.)

Werestrictendocrinetherapyintheneoadjuvantsettingtothetreatmentofpostmenopausalpatientswhoarenotsurgicalcandidatesatthetimeofpresentationandhavearelativeorabsolutecontraindicationtochemotherapy(ie,significantmedicalcomorbidities,advancedage,orpoorperformancestatus).(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Endocrinetherapy'and"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Eligibilityforprimarysurgery'.)

Followingsurgery(withorwithoutneoadjuvantsystemictherapy),allpatientswhoundergobreastconservingsurgeryshouldundergoadjuvantRTtomaximizelocoregionalcontrol.(See"Adjuvantradiationtherapyforwomenwithnewlydiagnosed,nonmetastaticbreastcancer".)

SomepatientstreatedbyamastectomyshouldreceivepostmastectomyRT.TheadministrationofadjuvantRTshouldbebasedupontheoriginalpretreatmentstage,regardlessofthepathologicresponsetoneoadjuvanttherapy.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis"and"Adjuvantradiationtherapyforwomenwithnewlydiagnosed,nonmetastaticbreastcancer".)

Theuseofchemotherapy,biologictherapy,and/orendocrinetherapyisguidedbythesameprinciplesusedtodeterminetreatmentforearlystagebreastcancer.(See'Adjuvanttherapy'above.)

Forpatientswhoreceivedneoadjuvantchemotherapy:

Patientswithhormonereceptorpositivebreastcancershouldreceiveadjuvantendocrinetherapy.Theselectionofendocrinetherapyismadeaccordingtomenopausalstatus.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Endocrinetherapy'.)

Patientswithhormonereceptornegativebreastcancershouldnotreceivefurthertreatmentprovidedtheycompletedtheplannedneoadjuvantchemotherapyregimen.Thesepatientsshouldbeginposttreatmentsurveillance.(See"Approachtothepatientfollowingtreatmentforbreastcancer",sectionon'Guidelinesforposttreatmentfollowup'.)

Patientswithhormonereceptornegativebreastcancerwhodidnotcompleteplannedneoadjuvant

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REFERENCES

1. KessonEM,AllardiceGM,GeorgeWD,etal.Effectsofmultidisciplinaryteamworkingonbreastcancersurvival:retrospective,comparative,interventionalcohortstudyof13722women.BMJ2012344:e2718.

2. EBCTCG(EarlyBreastCancerTrialists'CollaborativeGroup),McGaleP,TaylorC,etal.Effectofradiotherapyaftermastectomyandaxillarysurgeryon10yearrecurrenceand20yearbreastcancermortality:metaanalysisofindividualpatientdatafor8135womenin22randomisedtrials.Lancet2014383:2127.

3. GiulianoAE,HuntKK,BallmanKV,etal.Axillarydissectionvsnoaxillarydissectioninwomenwithinvasivebreastcancerandsentinelnodemetastasis:arandomizedclinicaltrial.JAMA2011305:569.

4. HaagensenCD,StoutAP.CARCINOMAOFTHEBREAST:II.CRITERIAOFOPERABILITY.AnnSurg1943118:859.

5. LeeSJ,SchoverLR,PartridgeAH,etal.AmericanSocietyofClinicalOncologyrecommendationsonfertilitypreservationincancerpatients.JClinOncol200624:2917.

6. HamakerME,BastiaannetE,EversD,etal.Omissionofsurgeryinelderlypatientswithearlystagebreastcancer.EurJCancer201349:545.

7. BrewsterAM,HortobagyiGN,BroglioKR,etal.Residualriskofbreastcancerrecurrence5yearsafteradjuvanttherapy.JNatlCancerInst2008100:1179.

8. NewmanLA.Epidemiologyoflocallyadvancedbreastcancer.SeminRadiatOncol200919:195.9. BastiaannetE,LiefersGJ,deCraenAJ,etal.Breastcancerinelderlycomparedtoyoungerpatientsinthe

Netherlands:stageatdiagnosis,treatmentandsurvivalin127,805unselectedpatients.BreastCancerResTreat2010124:801.

10. vandeWaterW,MarkopoulosC,vandeVeldeCJ,etal.Associationbetweenageatdiagnosisanddiseasespecificmortalityamongpostmenopausalwomenwithhormonereceptorpositivebreastcancer.JAMA2012307:590.

11. NicholAM,YerushalmiR,TyldesleyS,etal.Acasematchstudycomparingunilateralwithsynchronousbilateralbreastcanceroutcomes.JClinOncol201129:4763.

12. WeissenbacherTM,ZschageM,JanniW,etal.Multicentricandmultifocalversusunifocalbreastcancer:isthetumornodemetastasisclassificationjustified?BreastCancerResTreat2010122:27.

13. LynchSP,LeiX,ChavezMacGregorM,etal.Multifocalityandmulticentricityinbreastcancerandsurvivaloutcomes.AnnOncol201223:3063.

treatmentpriortosurgeryarecandidatesforfurtherchemotherapyinthepostoperative(oradjuvant)setting.

PatientswithHER2positivebreastcancershouldreceiveoneyearoftrastuzumabfollowingcompletionofsurgery.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'HER2directedtreatment'.)

Patientstreatedwithneoadjuvantendocrinetherapywhoundergosurgeryshouldcontinueendocrinetherapyintheadjuvantsetting.Whetherornottoadministeradjuvantchemotherapyshouldbeindividualized.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Endocrinetherapy'and"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Eligibilityforprimarysurgery'.)

ForsomepatientswithERpositivebreastcancer,inwhomsurgeryisnotanoptionorlifeexpectancyislimited,primaryhormonaltreatmentwitheithertamoxifenoranaromataseinhibitorwithoutsurgerycanbeused.(See'Olderwomen'aboveand"Generalprinciplesonthetreatmentofearlystageandlocallyadvancedbreastcancerinolderwomen",sectionon'Surgeryversusprimaryendocrinetherapyinwomenwithhormonereceptorpositivedisease'.)

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14. SwainSM,JeongJH,GeyerCEJr,etal.Longertherapy,iatrogenicamenorrhea,andsurvivalinearlybreastcancer.NEnglJMed2010362:2053.

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GRAPHICS

Tumornodemetastases(TNM)stagingsystemforcarcinomaofthebreast

Primarytumor(T)*TX Primarytumorcannotbeassessed

T0 Noevidenceofprimarytumor

Tis Carcinomainsitu

Tis(DCIS) Ductalcarcinomainsitu

Tis(LCIS) Lobularcarcinomainsitu

Tis(Paget's) Paget'sdisease(Pagetdisease)ofthenippleNOTassociatedwithinvasivecarcinomaand/orcarcinomainsitu(DCISand/orLCIS)intheunderlyingbreastparenchyma.CarcinomasinthebreastparenchymaassociatedwithPaget'sdiseasearecategorizedbasedonthesizeandcharacteristicsoftheparenchymaldisease,althoughthepresenceofPaget'sdiseaseshouldstillbenoted.

T1 Tumor20mmingreatestdimension

T1mi Tumor1mmingreatestdimension

T1a Tumor>1mmbut5mmingreatestdimension

T1b Tumor>5mmbut10mmingreatestdimension

T1c Tumor>10mmbut20mmingreatestdimension

T2 Tumor>20mmbut50mmingreatestdimension

T3 Tumor>50mmingreatestdimension

T4 Tumorofanysizewithdirectextensiontothechestwalland/ortotheskin(ulcerationorskinnodules)

T4a Extensiontothechestwall,notincludingonlypectoralismuscleadherence/invasion

T4b Ulcerationand/oripsilateralsatellitenodulesand/oredema(includingpeaud'orange)oftheskin,whichdonotmeetthecriteriaforinflammatorycarcinoma

T4c BothT4aandT4b

T4d Inflammatorycarcinoma

PosttreatmentypT.Theuseofneoadjuvanttherapydoesnotchangetheclinical(pretreatment)stage.Clinical(pretreatment)Twillbedefinedbyclinicalandradiographicfindings,whileypathologic(posttreatment)Twillbedeterminedbypathologicsizeandextension.TheypTwillbemeasuredasthelargestsinglefocusofinvasivetumor,withthemodifier"m"indicatingmultiplefoci.Themeasurementofthelargesttumorfocusshouldnotincludeareasoffibrosiswithinthetumorbed.

Regionallymphnodes(N)

Clinical

NX Regionallymphnodescannotbeassessed(eg,previouslyremoved)

N0 Noregionallymphnodemetastases

N1 MetastasestomovableipsilaterallevelI,IIaxillarylymphnode(s)

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N2 MetastasesinipsilaterallevelI,IIaxillarylymphnodesthatareclinicallyfixedormattedorinclinicallydetectedipsilateralinternalmammarynodesintheabsenceofclinicallyevidentaxillarylymphnodemetastases

N2a MetastasesinipsilaterallevelI,IIaxillarylymphnodesfixedtooneanother(matted)ortootherstructures

N2b MetastasesonlyinclinicallydetectedipsilateralinternalmammarynodesandintheabsenceofclinicallyevidentlevelI,IIaxillarylymphnodemetastases

N3 Metastasesinipsilateralinfraclavicular(levelIIIaxillary)lymphnode(s)withorwithoutlevelI,IIaxillarylymphnodeinvolvementorinclinicallydetectedipsilateralinternalmammarylymphnode(s)withclinicallyevidentlevelI,IIaxillarylymphnodemetastasesormetastasesinipsilateralsupraclavicularlymphnode(s)withorwithoutaxillaryorinternalmammarylymphnodeinvolvement

N3a Metastasesinipsilateralinfraclavicularlymphnode(s)

N3b Metastasesinipsilateralinternalmammarylymphnode(s)andaxillarylymphnode(s)

N3c Metastasesinipsilateralsupraclavicularlymphnode(s)

Pathologic(pN)**

pNX Regionallymphnodescannotbeassessed(eg,previouslyremoved,ornotremovedforpathologicstudy)

pN0 Noregionallymphnodemetastasisidentifiedhistologically

pN0(i) Noregionallymphnodemetastaseshistologically,negativeimmunohistochemistry(IHC)

pN0(i+) Malignantcellsinregionallymphnode(s)nogreaterthan0.2mm(detectedbyH&EorIHCincludingisolatedtumorcellclusters(ITC))

pN0(mol) Noregionallymphnodemetastaseshistologically,negativemolecularfindings(RTPCR)

pN0(mol+) Positivemolecularfindings(RTPCR),butnoregionallymphnodemetastasesdetectedbyhistologyorIHC

pN1 Micrometastasesormetastasesin13axillarylymphnodesand/orininternalmammarynodeswithmetastasesdetectedbysentinellymphnodebiopsybutnotclinicallydetected

pN1mi Micrometastases(greaterthan0.2mmand/ormorethan200cells,butnonegreaterthan2.0mm)

pN1a Metastasesin13axillarylymphnodes,atleastonemetastasisgreaterthan2.0mm

pN1b Metastasesininternalmammarynodeswithmicrometastasesormacrometastasesdetectedbysentinellymphnodebiopsybutnotclinicallydetected

pN1c Metastasesin13axillarylymphnodesandininternalmammarylymphnodeswithmicrometastasesormacrometastasesdetectedbysentinellymphnodebiopsybutnotclinicallydetected

pN2 Metastasesin49axillarylymphnodesorinclinicallydetectedinternalmammarylymphnodesintheabsenceofaxillarylymphnodemetastases

pN2a Metastasesin49axillarylymphnodes(atleastonetumordepositgreaterthan2.0mm)

pN2b Metastasesinclinicallydetectedinternalmammarylymphnodesintheabsenceofaxillarylymphnodemetastases

pN3 Metastasesintenormoreaxillarylymphnodesorininfraclavicular(levelIII

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axillary)lymphnodesorinclinicallydetectedipsilateralinternalmammarylymphnodesinthepresenceofoneormorepositivelevelI,IIaxillarylymphnodesorinmorethanthreeaxillarylymphnodesandininternalmammarylymphnodeswithmicrometastasesormacrometastasesdetectedbysentinellymphnodebiopsybutnotclinicallydetectedorinipsilateralsupraclavicularlymphnodes

pN3a Metastasesintenormoreaxillarylymphnodes(atleastonetumordepositgreaterthan2.0mm)ormetastasestotheinfraclavicular(levelIIIaxillarylymph)nodes

pN3b Metastasesinclinicallydetectedipsilateralinternalmammarylymphnodesinthepresenceofoneormorepositiveaxillarylymphnodesorinmorethanthreeaxillarylymphnodesandininternalmammarylymphnodeswithmicrometastasesormacrometastasesdetectedbysentinellymphnodebiopsybutnotclinicallydetected

pN3c Metastasesinipsilateralsupraclavicularlymphnodes

PosttreatmentypN

Posttreatmentyp"N"shouldbeevaluatedasforclinical(pretreatment)"N"methodsabove.Themodifier"sn"isusedonlyifasentinelnodeevaluationwasperformedaftertreatment.Ifnosubscriptisattached,itisassumedthattheaxillarynodalevaluationwasbyaxillarynodedissection(AND).

TheXclassificationwillbeused(ypNX)ifnoypposttreatmentSNorANDwasperformed

NcategoriesarethesameasthoseforpN

Distantmetastasis(M)M0 Noclinicalorradiographicevidenceofdistantmetastases

cM0(i+) Noclinicalorradiographicevidenceofdistantmetastases,butdepositsofmolecularlyormicroscopicallydetectedtumorcellsincirculatingblood,bonemarrow,orothernonregionalnodaltissuethatarenolargerthan0.2mminapatientwithoutsymptomsorsignsofmetastases

M1 Distantdetectablemetastasesasdeterminedbyclassicclinicalandradiographicmeansand/orhistologicallyprovenlargerthan0.2mm

PosttreatmentypMclassification.TheMcategoryforpatientstreatedwithneoadjuvanttherapyisthecategoryassignedintheclinicalstage,priortoinitiationofneoadjuvanttherapy.Identificationofdistantmetastasesafterthestartoftherapyincaseswherepretherapyevaluationshowednometastasesisconsideredprogressionofdisease.Ifapatientwasdesignatedtohavedetectabledistantmetastases(M1)beforechemotherapy,thepatientwillbedesignatedasM1throughout.

Anatomicstage/prognosticgroups0 Tis N0 M0

IA T1 N0 M0

IB T0 N1mi M0

T1 N1mi M0

IIA T0 N1 M0

T1 N1 M0

T2 N0 M0

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IIB T2 N1 M0

T3 N0 M0

IIIA T0 N2 M0

T1 N2 M0

T2 N2 M0

T3 N1 M0

T3 N2 M0

IIIB T4 N0 M0

T4 N1 M0

T4 N2 M0

IIIC AnyT N3 M0

IV AnyT AnyN M1

*TheTclassificationoftheprimarytumoristhesameregardlessofwhetheritisbasedonclinicalorpathologiccriteria,orboth.Designationshouldbemadewiththesubscript"c"or"p"modifiertoindicatewhethertheTclassificationwasdeterminedbyclinical(physicalexaminationorradiologic)orpathologicmeasurements,respectively.Ingeneral,pathologicdeterminationshouldtakeprecedenceoverclinicaldeterminationofTsize.Sizeshouldbemeasuredtothenearestmillimeter.IfthetumorsizeisslightlylessthanorgreaterthanacutoffforagivenTclassification,itisrecommendedthatthesizeberoundedtothemillimeterreadingthatisclosesttothecutoff.Multiplesimultaneousipsilateralprimarycarcinomasaredefinedasinfiltratingcarcinomasinthesamebreast,whicharegrosslyormacroscopicallydistinctandmeasurable.Tstageisbasedonlyonthelargesttumor.Thepresenceandsizesofthesmallertumor(s)shouldberecordedusingthe"(m)"modifier.InvasionofthedermisalonedoesnotqualifyasT4dimplingoftheskin,nippleretraction,oranyotherskinchangeexceptthosedescribedunderT4bandT4dmayoccurinT1,T2,orT3withoutchangingtheclassification.Thechestwallincludesribs,intercostalmuscles,andserratusanteriormuscle,butnotthepectoralismuscles.Inflammatorycarcinomaisaclinicalpathologicentitycharacterizedbydiffuseerythemaandedema(peaud'orange)involvingathirdormoreoftheskinofthebreast.Theseskinchangesareduetolymphedemacausedbytumoremboliwithindermallymphatics.Althoughdermallymphaticinvolvementsupportsthediagnosisofinflammatorybreastcancer,itisneithernecessarynorsufficient,intheabsenceofclassicalclinicalfindings,forthediagnosisofinflammatorybreastcancer.Ifacancerwasdesignatedasinflammatorybeforeneoadjuvantchemotherapy,thepatientwillbedesignatedtohaveinflammatorybreastcancerthroughout,evenifthepatienthascompleteresolutionofinflammatoryfindings.Clinicallydetectedisdefinedasdetectingbyimagingstudies(excludinglymphoscintigraphy)orbyclinicalexaminationandhavingcharacteristicshighlysuspiciousformalignancyorapresumedpathologicmacrometastasisbasedonfineneedleaspirationbiopsywithcytologicexamination.Confirmationofclinicallydetectedmetastaticdiseasebyfineneedleaspirationwithoutexcisionbiopsyisdesignatedwithan(f)suffix,forexample,cN3a(f).Excisionalbiopsyofalymphnodeorbiopsyofasentinelnode,intheabsenceofassignmentofapT,isclassifiedasaclinicalN,forexample,cN1.Informationregardingtheconfirmationofthenodalstatuswillbedesignatedinsitespecificfactorsasclinical,fineneedleaspiration,corebiopsy,orsentinellymphnodebiopsy.Pathologicclassification(pN)isusedforexcisionorsentinellymphnodebiopsyonlyinconjunctionwithapathologicTassignment.Classificationisbasedonaxillarylymphnodedissectionwithorwithoutsentinellymphnodebiopsy.

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Classificationbasedsolelyonsentinellymphnodebiopsywithoutsubsequentaxillarylymphnodedissectionisdesignated(sn)for"sentinelnode,"forexample,pN0(sn).**Isolatedtumorcellclusters(ITC)aredefinedassmallclustersofcellsnotgreaterthan0.2mm,orsingletumorcells,oraclusteroffewerthan200cellsinasinglehistologiccrosssection.ITCsmaybedetectedbyroutinehistologyorbyimmunohistochemical(IHC)methods.NodescontainingonlyITCsareexcludedfromthetotalpositivenodecountforpurposesofNclassificationbutshouldbeincludedinthetotalnumberofnodesevaluated.RTPCR:reversetranscriptase/polymerasechainreaction."Notclinicallydetected"isdefinedasnotdetectedbyimagingstudies(excludinglymphoscintigraphy)ornotdetectedbyclinicalexamination."Clinicallydetected"isdefinedasdetectedbyimagingstudies(excludinglymphoscintigraphy)orbyclinicalexaminationandhavingcharacteristicshighlysuspiciousformalignancyorapresumedpathologicmacrometastasisbasedonfineneedleaspirationbiopsywithcytologicexamination.Anatomicstage:M0includesM0(i+).ThedesignationpM0isnotvalidanyM0shouldbeclinical.IfapatientpresentswithM1priortoneoadjuvantsystemictherapy,thestageisconsideredStageIVandremainsStageIVregardlessofresponsetoneoadjuvanttherapy.Stagedesignationmaybechangedifpostsurgicalimagingstudiesrevealthepresenceofdistantmetastases,providedthatthestudiesarecarriedoutwithin4monthsofdiagnosisintheabsenceofdiseaseprogressionandprovidedthatthepatienthasnotreceivedneoadjuvanttherapy.Postneoadjuvanttherapyisdesignatedwiththe"y"prefix.Forpatientswithapathologiccompleteresponse(pCR)toneoadjuvanttherapy,nostagegroupisassigned(ie,yT0N0M0).T1includesT1mi.T0andT1tumorswithnodalmicrometastasesonlyareexcludedfromStageIIAandareclassifiedStageIB.

UsedwiththepermissionoftheAmericanJointCommitteeonCancer(AJCC),Chicago,Illinois.TheoriginalsourceforthismaterialistheAJCCCancerStagingManual,SeventhEdition(2010)publishedbySpringerNewYork,Inc.

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Disclosures:AlphonseTaghian,MD,PhDNothingtodisclose.MoatazNElGhamry,MDNothingtodisclose.SofiaDMerajver,MD,PhD[Breastcancer(Palbociclib)]AstraZeneca[Breastcancer(Circulatingtumorcells)].Speaker'sBureau:LillyOncology(Breastcancer).Consultant/AdvisoryBoards:Pfizer[Breastcancer(Palbociclib)].OtherFinancialInterest:JanssenR&D,LLC[Breastcancer(CellSearch)].DonSDizon,MD,FACPNothingtodisclose.Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.Conflictofinterestpolicy

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