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Overviewofthetreatmentofnewlydiagnosed,nonmetastaticbreastcancer
Authors
AlphonseTaghian,MD,PhD
MoatazNElGhamry,MD
SofiaDMerajver,MD,PhD

SectionEditor
DanielFHayes,MD

DeputyEditor
DonSDizon,MD,FACP

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2015.|Thistopiclastupdated:Aug25,2014.
INTRODUCTIONGlobally,breastcanceristhemostfrequentlydiagnosedcancerandtheleadingcauseof
cancerdeathinwomen.IntheUnitedStates,breastcanceristhemostcommonlydiagnosedcancerandthe
secondmostcommoncauseofcancerdeathinwomen.Inaddition,breastcanceristheleadingcauseofdeathin
womenages40to49years.
Breastcanceristreatedwithamultidisciplinaryapproachinvolvingsurgicaloncology,radiationoncology,and
medicaloncology,whichhasbeenassociatedwithareductioninbreastcancermortality[1].
Thistopicwillprovideanoverviewoftheinitialtreatmentofbreastcancerandposttreatmentsurveillance.The
epidemiology,clinicalmanifestations,diagnosis,stagingofbreastcancer,andspecificdiscussionsofthe
multimodalitytreatmentsforearlybreastcancerandtheapproachtometastaticdiseasearediscussedelsewhere.
(See"Clinicalfeatures,diagnosis,andstagingofnewlydiagnosedbreastcancer"and"Systemictreatmentfor
metastaticbreastcancer:Generalprinciples"and"Metastaticbreastcancer:Localtreatment".)
Becauseductalcarcinomainsitu(DCIS)andinvasivebreastcanceraremanageddifferently,wewillrestrict
discussioninthistopictoinvasivebreastcancer.AdiscussiononDCISiscoveredseparately.(See"Breast
ductalcarcinomainsitu:Epidemiology,clinicalmanifestations,anddiagnosis"and"Ductalcarcinomainsitu:
Treatmentandprognosis".)
PATIENTSTRATIFICATIONThevastmajorityofpatientswithnewlydiagnosedbreastcancerintheUnited
Statesanddevelopedcountrieshavenoevidenceofmetastaticdisease.Forthesepatients,thetreatment
approachdependsonthestageatpresentation.Fortreatmentpurposes,breastcancerischaracterizedusingthe
Tumor,Node,Metastasessystem(TNM)(table1):
EarlystageThisincludespatientswithclinicalstageI,IIA,orasubsetofstageIIBdisease(T2N1).
LocallyadvancedThisincludesasubsetofpatientswithclinicalstageIIBdisease(T3N0)andpatients
withstageIIIAtoIIICdisease.
Approximately5percentofpatientswillhavesimultaneousmetastaticdiseaseidentifiedattheinitialpresentation
(denovostageIVbreastcancer).Thetreatmentapproachtothesepatientsisdiscussedseparately.(See"Roleof
breastsurgeryforstageIVbreastcancer"and"Systemictreatmentformetastaticbreastcancer:General
principles".)
EARLYSTAGEBREASTCANCERIngeneral,patientswithearlystagebreastcancerundergoprimary
surgery(lumpectomyormastectomy)tothebreastandregionalnodeswithorwithoutradiationtherapy(RT).
Followingdefinitivelocaltreatment,adjuvantsystemictherapymaybeofferedbasedonprimarytumor
characteristics,suchastumorsize,grade,numberofinvolvedlymphnodes,thestatusofestrogen(ER)and
progesterone(PR)receptors,andexpressionofthehumanepidermalgrowthfactor2(HER2)receptor.
BreastconservingtherapyBreastconservingtherapy(BCT)iscomprisedofbreastconservingsurgery(BCS,
ie,lumpectomy)plusradiationtherapy(RT).ThegoalsofBCTaretoprovidethesurvivalequivalentof
mastectomy,acosmeticallyacceptablebreast,andalowrateofrecurrenceinthetreatedbreast.BCTallows
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patientswithinvasivebreastcancertopreservetheirbreastwithoutsacrificingoncologicoutcome.Successful
BCTrequirescompletesurgicalremovalofthetumor(withnegativesurgicalmargins)followedbymoderatedose
RTtoeradicateanyresidualdisease.(See"Breastconservingtherapy".)
CriteriathatprecludeBCTinclude(see"Breastconservingtherapy",sectionon'PatientselectionforBCT'):
Multicentricdisease
Largetumorsizeinrelationtobreast
Presenceofdiffusemalignantappearingcalcificationsonimaging(ie,mammogramormagneticresonance
imaging[MRI])
PriorhistoryofchestRT(eg,mantleradiationforHodgkindisease)
Pregnancy
Persistentlypositivemarginsdespiteattemptsatreexcision
ForpatientswhodesireBCTbutarenotcandidatesatthetimeofpresentation,analternativeapproachistheuse
ofneoadjuvanttherapy,whichmayallowforBCSwithoutcompromisingsurvivaloutcomes.(See'Neoadjuvant
systemictherapy'below.)
MastectomyAmastectomyisindicatedforpatientswhoarenotcandidatesforBCTandthosewhoprefer
mastectomy.(See"Mastectomy:Indications,types,andconcurrentaxillarylymphnodemanagement",sectionon
'Selectioncriteriaformastectomy'.)
RoleofRTPostmastectomyRTisindicatedforpatientsathighriskforlocalrecurrence,suchasthose
withcancerinvolvingthedeepmarginsandpathologicallyinvolvedaxillarylymphnodes.Ifthelikelihoodof
postmastectomyRTishighpreoperatively,thismayaffectthechoiceofmastectomytype,thechoiceofthe
reconstructiveapproach,andoptimaltimingofthebreastreconstruction(immediateversusdelayed).Basedupon
theEarlyBreastCancerTrialistsCollaborativeGroupmetaanalysisof3786womenwithinvasivebreastcancer
undergoinganaxillarydissectionandmastectomy,therewasareductioninrecurrencesfornodepositivewomen
([n=1314,onetothreenodespositive]and[n=1772,fourormorenodespositive])undergoingpostmastectomy
radiation,butnotfornodenegativewomen[2].
Thus,preoperativecoordinationofcareassuresthebestoutcome.Inmanycenters,thisisaccomplishedbymulti
disciplinarybreastclinics.(See"Adjuvantradiationtherapyforwomenwithnewlydiagnosed,nonmetastatic
breastcancer",sectionon'Patientstreatedwithmastectomy'.)
EvaluationoftheaxillarynodesTheriskformetastasestotheaxillarynodesisrelatedtotumorsizeand
location,histologicgrade,andthepresenceoflymphaticinvasionwithintheprimarytumor.Althoughinternal
mammaryorsupraclavicularnodesmaybeinvolvedattheinitialpresentation,theyrarelyoccurintheabsenceof
axillarynodeinvolvement.(See"Managementoftheregionallymphnodesinbreastcancer",sectionon'Internal
mammarylymphnodes'and"Managementoftheregionallymphnodesinbreastcancer",sectionon
'Supraclavicularlymphnodes'.)
Theevaluationoftheregionalnodesdependsonwhetheraxillaryinvolvementissuspectedpriortosurgery:
Forpatientspresentingwithclinicallysuspiciousaxillarylymphnodes,apreoperativeworkupincludingultrasound
plusfineneedleaspiration(FNA)orcorebiopsycanhelptodeterminethebestsurgicalapproach.
Forpatientswithapositivebiopsy,anaxillarynodedissectionshouldbeperformedatthetimeofbreast
surgery.(See"Techniqueofaxillarylymphnodedissection".)
Forpatientspresentingwithanegativebiopsy,nofurtherworkupisrequiredpriortosurgery.Thesepatients
shouldundergoasentinellymphnodebiopsy(SLNB)atthetimeofsurgery.(See"Diagnosis,stagingand
theroleofsentinellymphnodebiopsyinthenodalevaluationofbreastcancer"and"Sentinellymphnode
biopsyinbreastcancer:Techniques".)
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PatientswithaclinicallynegativeaxillaryexaminationshouldundergoaSLNBatthetimeofsurgery.Further
evaluationoftheregionalnodesdependsonthefindingsatSLNB.
Patientswhohavelessthanthreepathologicallyinvolvedsentinelnodesmaynotrequireacompleteaxillary
nodedissection[3].However,whetherornotpatientswiththreeormorepathologicallyinvolvedsentinel
nodesshouldundergoanaxillarynodedissectionisbestdeterminedonanindividualizedbasis,takinginto
accountallothertumorriskfactorsandthepatientsperformancestatusandcomorbidities.(See"Diagnosis,
stagingandtheroleofsentinellymphnodebiopsyinthenodalevaluationofbreastcancer".)
AdjuvanttherapySystemictherapyreferstothemedicaltreatmentofbreastcancerusingendocrinetherapy,
chemotherapy,and/orbiologictherapy.(See"Adjuvantchemotherapyforhormonereceptorpositiveornegative,
HER2negativebreastcancer"and"AdjuvantmedicaltherapyforHER2positivebreastcancer"and"Adjuvant
endocrinetherapyfornonmetastatic,hormonereceptorpositivebreastcancer".)
Tumorcharacteristicspredictwhichpatientsarelikelytobenefitfromspecifictypesoftherapy.Forexample,
hormonereceptorpositivepatientsbenefitfromtheuseofendocrinetherapy.Inaddition,patientswithhuman
epidermalgrowthfactorreceptor2(HER2)positivecancersbenefitfromtreatmentusingHER2directedtreatment.
(See"Prognosticandpredictivefactorsinearly,nonmetastaticbreastcancer".)
Forpatientswithearlystagebreastcancer,treatmentisbasedontumorcharacteristics,patientstatus,and
patientpreferences:
Patientswithhormonereceptorpositivebreastcancershouldreceiveendocrinetherapy.Whethertheyalso
shouldreceiveadjuvantchemotherapydependsonpatientandtumorcharacteristics.(See"Adjuvant
endocrinetherapyfornonmetastatic,hormonereceptorpositivebreastcancer"and"Adjuvantchemotherapy
forhormonereceptorpositiveornegative,HER2negativebreastcancer",sectionon'Indicationsfor
treatment'.)
Weofferchemotherapytopatientswithearlystagehormonereceptorpositivecancersthathavehigh
riskcharacteristics,suchashighgradetumor,largetumorsize(2cm),pathologicallyinvolvedlymph
nodes,and/orhigh21generecurrencescore(31).
Intheabsenceofhighriskfeatures,weprefernottoadministerchemotherapy.
ForpatientswithER/PRandHER2negativedisease(triplenegativebreastcancer),weprefertoadminister
adjuvantchemotherapyifthetumorsizeis0.5cm.Becausethesepatientsarenotcandidatesforendocrine
therapyortreatmentwithHER2directedagents,chemotherapyistheironlyoptionforadjuvanttreatment,
followingorbeforeradiotherapy.Patientswithatriplenegativebreastcancer<0.5cminsizemayforego
adjuvantchemotherapyinmostcases,duetominimal,ifany,survivaladvantage.(See"Epidemiology,risk
factorsandtheclinicalapproachtoER/PRnegative,HER2negative(Triplenegative)breastcancer"and
"Adjuvantchemotherapyforhormonereceptorpositiveornegative,HER2negativebreastcancer".)
PatientswithHER2positivebreastcancerwithatumorsize>1cmshouldreceiveacombinationof
chemotherapyplusHER2directedtherapy.Themanagementofsmall(1cm)HER2positivebreastcancers
iscontroversial.(See"AdjuvantmedicaltherapyforHER2positivebreastcancer",sectionon'Patient
eligibility'.)
Followingchemotherapy,patientswithERpositivediseaseshouldalsoreceiveadjuvantendocrinetherapy.
(See"AdjuvantmedicaltherapyforHER2positivebreastcancer"and"Adjuvantendocrinetherapyfornon
metastatic,hormonereceptorpositivebreastcancer",sectionon'PatientswithHER2positivetumors'.)
LOCALLYADVANCEDBREASTCANCERLocallyadvancedbreastcancerisbestmanagedwith
multimodalitytherapyemployingsystemicandlocoregionaltherapy.(See'Patientstratification'above.)
NeoadjuvantsystemictherapyMostpatientswithlocallyadvancedbreastcancershouldreceiveneoadjuvant
systemictherapy.Thegoaloftreatmentistoinduceatumorresponsebeforesurgeryandenablebreast
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conservation.
Neoadjuvanttherapyresultsinlongtermdistantdiseasefreesurvivalandoverallsurvival(OS)comparabletothat
achievedwithprimarysurgeryfollowedbyadjuvantsystemictherapy.(See"Neoadjuvanttherapyforbreast
cancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Patientselection'.)
Ourapproachtotheselectionoftreatmentintheneoadjuvantsettingisoutlinedbelow:
Formostpatientswithhormonereceptorpositivedisease,werecommendchemotherapyintheneoadjuvant
settingratherthanendocrinetherapy.Chemotherapyisassociatedwithhigherresponseratesinashorter
timeperiod.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeutic
options",sectionon'Patientselection'.)
Forpatientswithhumanepidermalgrowthfactorreceptor2(HER2)positivebreastcancer,aHER2directed
agent(eg,trastuzumabwithorwithoutpertuzumab)shouldbeaddedtothechemotherapyregimen.(See
"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",section
on'HER2directedtherapy'.)
Werestrictendocrinetherapyintheneoadjuvantsettingtothetreatmentofpostmenopausalpatientswith
hormonereceptorpositivediseasewhoarenotsurgicalcandidates(regardlessoftumorsize)witharelative
orabsolutecontraindicationtochemotherapy(ie,significantmedicalcomorbidities,advancedage,orpoor
performancestatus).(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,and
therapeuticoptions",sectionon'Endocrinetherapy'and"Neoadjuvanttherapyforbreastcancer:Rationale,
pretreatmentevaluation,andtherapeuticoptions",sectionon'Patientselection'.)
SurgicalapproachafterneoadjuvanttreatmentAllpatientsshouldundergosurgeryfollowingneoadjuvant
systemictherapy,eveniftheyhaveacompleteclinicaland/orradiologicalresponse.Inaddition,patientswho
experienceprogressionwhileonneoadjuvantsystemictherapyshouldproceedwithsurgery,ratherthanswitching
thechemotherapyregimen.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequent
treatment,andprognosis",sectionon'Definitivesurgicaltreatment'.)
PrimarytumorThechoicebetweenbreastconservationandmastectomyafterneoadjuvanttreatmentis
dependentonthetreatmentresponseandpatientcharacteristics(eg,breastsizeinrelationtoresidualtumorsize).
Similarcriteriausedinthetreatmentofearlystagebreastcancerareapplied.However,patientswhopresentwith
alarge(ie,T4)breastlesionshouldundergoamastectomyfollowingneoadjuvanttreatment.(See'Breast
conservingtherapy'aboveand'Mastectomy'above.)
RegionalnodesAllpatientsrequireasurgicalevaluationoftheregionalnodesfollowingneoadjuvant
treatment.(See'Evaluationoftheaxillarynodes'aboveand"Neoadjuvantsystemictherapyforbreastcancer:
Response,subsequenttreatment,andprognosis",sectionon'Nodalevaluation'.)
PrimarysurgeryAlthoughsomepatientsmaybecandidatesforprimarysurgeryatpresentation,patientswith
locallyadvanceddiseasehaveanextremelyhighriskoflocalrecurrenceanddistantmetastases[4].Asaresult,
weprefertotreatpatientswithlocallyadvancedbreastcancerwithneoadjuvantsystemictherapyfirst.
Forpatientswhoproceedwithprimarysurgery,basedonpathologicalresults,postoperativeradiationtherapy(RT)
andadjuvanttreatmentshouldbeadministered.(See"Radiationtherapytechniquesfornewlydiagnosed,non
metastaticbreastcancer"and'Adjuvanttherapy'below.)
AdjuvanttherapyTheuseofpostoperative(adjuvant)systemictherapyisguidedbythepatientsclinical
statusandtumorcharacteristics:
Patientswhodidnotreceiveneoadjuvantsystemictherapyshouldreceiveadjuvanttreatment.Theuseof
chemotherapy,biologictherapy,and/orendocrinetherapyisguidedbythesameprinciplesusedtodetermine
treatmentforearlystagebreastcancer.(See'Adjuvanttherapy'above.)
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Forpatientswhoreceivedthefullcourseofplannedneoadjuvantchemotherapy(see"Neoadjuvantsystemic
therapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Chemotherapy'):
Patientswithhormonereceptorpositivebreastcancershouldreceiveendocrinetherapytoreducethe
riskofbreastcancerrecurrenceandbreastcancerrelatedmortality.Thereisnoevidencethatthe
additionoffurtherchemotherapyintheformofadjuvanttreatmentimprovesOS.Theselectionof
endocrinetherapyismadeaccordingtomenopausalstatus.(See"Neoadjuvantsystemictherapyfor
breastcancer:Response,subsequenttreatment,andprognosis",sectionon'Endocrinetherapy'.)
Patientswithhormonereceptornegativebreastcancerwouldtypicallynotreceivefurtherchemotherapy
intheadjuvantsetting,asthereisnoevidencethattheadditionofadjuvantchemotherapyimproves
OS.Thesepatientsshouldbeginposttreatmentsurveillance.(See"Approachtothepatientfollowing
treatmentforbreastcancer",sectionon'Guidelinesforposttreatmentfollowup'.)
Insomeexceptionalcaseswherethetumorprogressedduringneoadjuvanttherapyorifthecomplete
neoadjuvanttherapycouldnotbedeliveredatthenormallevelsofintensity,adjuvantchemotherapy
shouldbediscussedandconsidered.
PatientswithHER2positivebreastcancershouldreceiveoneyearoftrastuzumabfollowing
completionofsurgerywithouttheadditionoffurtherchemotherapy.Thisrecommendationisbasedon
studiesofadjuvantchemotherapywithorwithouttrastuzumabthatdemonstratedthattheadditionof
oneyearoftrastuzumabsignificantlyimprovesdiseasefreesurvivalandOS.(See"Neoadjuvant
systemictherapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon
'HER2directedtreatment'.)
Patientstreatedwithneoadjuvantendocrinetherapywhoundergosurgeryshouldcontinueendocrinetherapyinthe
adjuvantsetting.Whetherornottoadministeradjuvantchemotherapyshouldbeindividualized.(See"Neoadjuvant
therapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Objectives'.)
SPECIALCONSIDERATIONS
FertilitypreservationCliniciansshoulddiscusswithpatientstheriskofinfertilityandpossibleinterventionsto
preservefertilitypriortoinitiatingpotentiallygonadotoxictherapy.Thisdiscussionshouldoccursoonafter
diagnosis,sincesomeinterventionstopreservefertilitytaketimeandcoulddelaythestartoftreatment.Thisis
consistentwithguidancefromtheAmericanSocietyofClinicalOncology[5].Thetopicoffertilitypreservationis
coveredindetailseparately.(See"Fertilitypreservationinpatientsundergoinggonadotoxictreatmentorgonadal
resection".)
OlderwomenForsomepatientswithestrogenreceptor(ER)positivebreastcancer,inwhomsurgeryisnotan
optionorlifeexpectancyislimited,primaryhormonaltreatmentwitheithertamoxifenoranaromataseinhibitor
withoutsurgeryorradiationtherapy(RT)canbeused[6].Weprefertoindividualizetreatmentbasedonthe
presenceofmedicalcomorbiditiesandpatientandclinicianpreference.(See"Generalprinciplesonthetreatment
ofearlystageandlocallyadvancedbreastcancerinolderwomen",sectionon'Surgeryversusprimaryendocrine
therapyinwomenwithhormonereceptorpositivedisease'.)
MalebreastcancerThetopicofmalebreastcancerisdiscussedseparately.(See"Breastcancerinmen".)
BreastcancerinpregnancyThetreatmentofbreastcancerinpregnancyisdiscussedseparately.(See
"Gestationalbreastcancer:Treatment".)
PROGNOSISThemajorityofbreastcancerrecurrencesoccurwithinthefirstfiveyearsofdiagnosis,
particularlywithhormonereceptornegativedisease.However,somerecurrencesoccurmuchlater.Inonestudyof
patientswithstageI,II,orIIIbreastcancerwhowerewithoutevidenceofdiseasefiveyearsoutfromtheoriginal
diagnosis,therecurrencerisksinthesubsequentfiveandtenyearswerestill11and19percent,respectively[7].
(See"Patternsofrelapseandlongtermcomplicationsoftherapyinbreastcancersurvivors",sectionon'Relapse
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patterns'.)
Patientswithearlystagebreastcancerhaveabetterprognosisthanthosepatientsdiagnosedwithlocally
advanceddisease.AccordingtoTumor,Nodes,Metastases(TNM)stage,fiveyearrelativesurvivalratesbystage
forpatientspresentingwithstageI,IIA,IIB,IIIA,IIIB,andIVdiseasewere95,85,70,52,48,and18percent,
respectively[8].Bothyounger(age<35years)andolderage(age65years)atdiagnosisareassociatedwitha
worseprognosis[9,10].(See"Prognosticandpredictivefactorsinearly,nonmetastaticbreastcancer".)
Althoughthereissomecontroversyregardingtheprognosisofpatientswhopresentwithsynchronousbreast
cancer(ie,bilateralbreastcancerdiagnosedsimultaneously),arecentstudysuggeststheirprognosisisno
differentfromthatofpatientspresentingwithunilateralbreastcancer[11].
Theimpactofmultifocal(ie,invasivetumorsidentifiedwithinthesamebreastquadrant)ormulticentric(ie,
invasivetumorsidentifiedinseparatebreastquadrants)tumorsonprognosisiscontroversial,withsomeevidence
thattheyareassociatedwithapoorprognosis[12]andotherdatasuggestingtheydonotimpactprognosis[13].
Currently,theTNMstagingsystemdoesnotassignindependentvaluetomultifocalityormulticentricityanduses
thediameterofthelargestlesiontoassignTstage.
ResumptionofmensesForpremenopausalpatientswhoreceivedadjuvantchemotherapy,chemotherapy
inducedamenorrheaandlackofresumptionofmenstrualcyclesafterchemotherapyisassociatedwithimproved
survival,aftercontrollingforstandardprognosticvariables,particularlyforhormonereceptorpositivedisease[14].
POSTTREATMENTSURVEILLANCECancersurvivorswhohavecompletedtreatmentforbreastcancer
shouldundergoregularfollowup.Annualmammographyshouldalsobeperformedinpatientswhounderwent
breastconservingtherapy(BCT).Theroutineuseofbreastmagneticresonanceimaging(MRI)orwholebreast
ultrasoundisnotrecommendedforbreastcancersurvivorsbecauseofalackofevidencetoinformtheirrolein
thispopulation.Inaddition,laboratorytestsandwholebodyimaginginasymptomaticcancersurvivorsisnot
recommended.(See"Patternsofrelapseandlongtermcomplicationsoftherapyinbreastcancersurvivors",
sectionon'Longtermadverseeffectsofprimarytherapy'and"Approachtothepatientfollowingtreatmentfor
breastcancer",sectionon'Guidelinesforposttreatmentfollowup'.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Breastcancer(TheBasics)"and"Patientinformation:Choosing
treatmentforearlystagebreastcancer(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Breastcancerguidetodiagnosisandtreatment(Beyond
theBasics)"and"Patientinformation:Factorsthatmodifybreastcancerriskinwomen(BeyondtheBasics)"
and"Patientinformation:Earlystagebreastcancertreatmentinpostmenopausalwomen(Beyondthe
Basics)"and"Patientinformation:Earlystagebreastcancertreatmentinpremenopausalwomen(Beyondthe
Basics)"and"Patientinformation:SurgicalproceduresforbreastcancerMastectomyandbreast
conservingtherapy(BeyondtheBasics)"and"Patientinformation:AdjuvantmedicaltherapyforHER2
positivebreastcancer(BeyondtheBasics)"and"Patientinformation:Locallyadvancedandinflammatory
breastcancer(BeyondtheBasics)")
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SUMMARY
PatientstratificationPatientswithanewdiagnosisofbreastcancercanbestratifiedbytheirextentofdisease
(see'Patientstratification'above):
PatientswithclinicalstageI,IIA,orasubsetofstageIIBdisease(T2N1)areclassifiedashavingearly
stagebreastcancer.
PatientswithaT3tumorwithoutnodalinvolvement(T3N0,asubsetofpatientswithclinicalstageIIB
disease)andthosewhopresentwithstageIIIAtoIIICdiseaseareclassifiedashavinglocallyadvanced
breastcancer.
Approximately5percentofpatientswillpresentwithdistantmetastases(stageIV)atdiagnosis.
Earlystagebreastcancer
Thesurgicalapproachtotheprimarytumordependsonthesizeofthetumor,whetherornotmultifocal
diseaseispresent,andthesizeofthebreast.Theoptionsincludebreastconservingtherapy(breast
conservingsurgeryplusradiationtherapy[RT])ormastectomy(withorwithoutRT).Bothapproachesresult
inequivalentcancerspecificoutcomes.(See'Earlystagebreastcancer'aboveand"Breastconserving
therapy"and"Mastectomy:Indications,types,andconcurrentaxillarylymphnodemanagement".)
Theriskformetastaticdiseaseintheregionalnodesisrelatedtotumorsize,histologicgrade,andthe
presenceoflymphaticinvasionwithintheprimarytumor.Althoughinternalmammaryorsupraclavicular
nodesmayalsobeinvolvedattheinitialpresentation,theyrarelyoccurintheabsenceofaxillarynode
involvement.Thesurgicalapproachtotheregionalnodesdependsontheclinicalstatusoftheaxilla(see
'Evaluationoftheaxillarynodes'above):
Forpatientspresentingwithclinicallysuspiciousaxillarynodes,apreoperativeworkupincluding
ultrasoundpluslymphnodebiopsycanhelptodeterminethebestsurgicalapproach.Ifthelymphnode
biopsyispositive,anaxillarynodedissectionshouldbeperformed.Ifthelymphnodebiopsyis
negative,asentinellymphnodebiopsy(SLNB)atthetimeofsurgeryshouldbeperformed.(See
"Managementoftheregionallymphnodesinbreastcancer",sectionon'Axillaryultrasound'and
"Managementoftheregionallymphnodesinbreastcancer",sectionon'Axillarydissection'and
"Managementoftheregionallymphnodesinbreastcancer",sectionon'Sentinellymphnodebiopsy'.)
Patientswhopresentwithaclinicallynegativeaxilladonotrequireapreoperativeworkup.These
patientsshouldundergoanSLNBatthetimeofdefinitivebreastsurgery.Patientswhohave<3
pathologicallyinvolvedsentinelnodesbySLNBmightnotrequireanaxillarynodedissection.Whether
ornotpatientswith3pathologicallyinvolvedsentinelnodesinvolvedshouldundergoanaxillarynode
dissectionisbestdeterminedonanindividualizedbasis,takingintoaccountallothertumorriskfactors
andthepatientsperformancestatusandcomorbidities.(See"Diagnosis,stagingandtheroleof
sentinellymphnodebiopsyinthenodalevaluationofbreastcancer".)
Tumorcharacteristicsareusedtoselectadjuvanttreatmentforpatientswithbreastcancer.(See'Adjuvant
therapy'above.)
Patientswithhormonereceptorpositivebreastcancershouldreceiveadjuvantendocrinetherapy.The
roleofadjuvantchemotherapyinthesepatientsrequiresariskstratifiedapproachthattakesinto
accountpatientandtumorcharacteristicstoselectpatientswhoshouldreceiveadjuvant
chemotherapy.(See"Adjuvantendocrinetherapyfornonmetastatic,hormonereceptorpositivebreast
cancer"and"Adjuvantchemotherapyforhormonereceptorpositiveornegative,HER2negativebreast
cancer",sectionon'Indicationsfortreatment'.)
Forpatientswithestrogenreceptor(ER),progesteronereceptor(PR),andhumanepidermalgrowth
factorreceptor2(HER2)negativedisease(triplenegativebreastcancer),weprefertoadminister
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adjuvantchemotherapyifthetumorsizeis>0.5cm.(See"Epidemiology,riskfactorsandtheclinical
approachtoER/PRnegative,HER2negative(Triplenegative)breastcancer"and"Adjuvant
chemotherapyforhormonereceptorpositiveornegative,HER2negativebreastcancer".)
PatientswithHER2positivebreastcancer>1cminsizeshouldreceiveacombinationof
chemotherapyplusHER2directedtherapy.Followingchemotherapy,patientswithERpositivedisease
shouldalsoreceiveadjuvantendocrinetherapy.(See"AdjuvantmedicaltherapyforHER2positive
breastcancer"and"Adjuvantendocrinetherapyfornonmetastatic,hormonereceptorpositivebreast
cancer",sectionon'PatientswithHER2positivetumors'.)
Locallyadvancedbreastcancer
Mostpatientswithlocallyadvanced,inoperablebreastcancershouldreceiveneoadjuvantsystemictherapy
ratherthanproceedingwithprimarysurgery.Thesepatientsareusuallynotcandidatesforbreast
conservationattheirinitialpresentation.Neoadjuvanttreatmentimprovestherateofbreastconservation
withoutcompromisingsurvivaloutcomes.(See'Neoadjuvantsystemictherapy'above.)
Formostpatients,werecommendchemotherapyintheneoadjuvantsettingratherthanendocrine
therapy.Chemotherapyisassociatedwithhigherresponseratesinafastertimeframe.AHER2
directedagent(ie,trastuzumab)shouldbeaddedtothechemotherapyregimenfortumorsthatare
HER2positive.(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,and
therapeuticoptions",sectionon'Eligibilityforprimarysurgery'.)
Werestrictendocrinetherapyintheneoadjuvantsettingtothetreatmentofpostmenopausalpatients
whoarenotsurgicalcandidatesatthetimeofpresentationandhavearelativeorabsolute
contraindicationtochemotherapy(ie,significantmedicalcomorbidities,advancedage,orpoor
performancestatus).(See"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,
andtherapeuticoptions",sectionon'Endocrinetherapy'and"Neoadjuvanttherapyforbreastcancer:
Rationale,pretreatmentevaluation,andtherapeuticoptions",sectionon'Eligibilityforprimarysurgery'.)
Followingsurgery(withorwithoutneoadjuvantsystemictherapy),allpatientswhoundergobreastconserving
surgeryshouldundergoadjuvantRTtomaximizelocoregionalcontrol.(See"Adjuvantradiationtherapyfor
womenwithnewlydiagnosed,nonmetastaticbreastcancer".)
SomepatientstreatedbyamastectomyshouldreceivepostmastectomyRT.Theadministrationofadjuvant
RTshouldbebasedupontheoriginalpretreatmentstage,regardlessofthepathologicresponseto
neoadjuvanttherapy.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequent
treatment,andprognosis"and"Adjuvantradiationtherapyforwomenwithnewlydiagnosed,nonmetastatic
breastcancer".)
Theuseofchemotherapy,biologictherapy,and/orendocrinetherapyisguidedbythesameprinciplesused
todeterminetreatmentforearlystagebreastcancer.(See'Adjuvanttherapy'above.)
Forpatientswhoreceivedneoadjuvantchemotherapy:
Patientswithhormonereceptorpositivebreastcancershouldreceiveadjuvantendocrinetherapy.The
selectionofendocrinetherapyismadeaccordingtomenopausalstatus.(See"Neoadjuvantsystemic
therapyforbreastcancer:Response,subsequenttreatment,andprognosis",sectionon'Endocrine
therapy'.)
Patientswithhormonereceptornegativebreastcancershouldnotreceivefurthertreatmentprovided
theycompletedtheplannedneoadjuvantchemotherapyregimen.Thesepatientsshouldbegin
posttreatmentsurveillance.(See"Approachtothepatientfollowingtreatmentforbreastcancer",
sectionon'Guidelinesforposttreatmentfollowup'.)
Patientswithhormonereceptornegativebreastcancerwhodidnotcompleteplannedneoadjuvant
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treatmentpriortosurgeryarecandidatesforfurtherchemotherapyinthepostoperative(oradjuvant)
setting.
PatientswithHER2positivebreastcancershouldreceiveoneyearoftrastuzumabfollowing
completionofsurgery.(See"Neoadjuvantsystemictherapyforbreastcancer:Response,subsequent
treatment,andprognosis",sectionon'HER2directedtreatment'.)
Patientstreatedwithneoadjuvantendocrinetherapywhoundergosurgeryshouldcontinueendocrinetherapy
intheadjuvantsetting.Whetherornottoadministeradjuvantchemotherapyshouldbeindividualized.(See
"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,andtherapeuticoptions",section
on'Endocrinetherapy'and"Neoadjuvanttherapyforbreastcancer:Rationale,pretreatmentevaluation,and
therapeuticoptions",sectionon'Eligibilityforprimarysurgery'.)
ForsomepatientswithERpositivebreastcancer,inwhomsurgeryisnotanoptionorlifeexpectancyis
limited,primaryhormonaltreatmentwitheithertamoxifenoranaromataseinhibitorwithoutsurgerycanbe
used.(See'Olderwomen'aboveand"Generalprinciplesonthetreatmentofearlystageandlocally
advancedbreastcancerinolderwomen",sectionon'Surgeryversusprimaryendocrinetherapyinwomen
withhormonereceptorpositivedisease'.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. KessonEM,AllardiceGM,GeorgeWD,etal.Effectsofmultidisciplinaryteamworkingonbreastcancer
survival:retrospective,comparative,interventionalcohortstudyof13722women.BMJ2012344:e2718.
2. EBCTCG(EarlyBreastCancerTrialists'CollaborativeGroup),McGaleP,TaylorC,etal.Effectof
radiotherapyaftermastectomyandaxillarysurgeryon10yearrecurrenceand20yearbreastcancer
mortality:metaanalysisofindividualpatientdatafor8135womenin22randomisedtrials.Lancet2014
383:2127.
3. GiulianoAE,HuntKK,BallmanKV,etal.Axillarydissectionvsnoaxillarydissectioninwomenwith
invasivebreastcancerandsentinelnodemetastasis:arandomizedclinicaltrial.JAMA2011305:569.
4. HaagensenCD,StoutAP.CARCINOMAOFTHEBREAST:II.CRITERIAOFOPERABILITY.AnnSurg
1943118:859.
5. LeeSJ,SchoverLR,PartridgeAH,etal.AmericanSocietyofClinicalOncologyrecommendationson
fertilitypreservationincancerpatients.JClinOncol200624:2917.
6. HamakerME,BastiaannetE,EversD,etal.Omissionofsurgeryinelderlypatientswithearlystagebreast
cancer.EurJCancer201349:545.
7. BrewsterAM,HortobagyiGN,BroglioKR,etal.Residualriskofbreastcancerrecurrence5yearsafter
adjuvanttherapy.JNatlCancerInst2008100:1179.
8. NewmanLA.Epidemiologyoflocallyadvancedbreastcancer.SeminRadiatOncol200919:195.
9. BastiaannetE,LiefersGJ,deCraenAJ,etal.Breastcancerinelderlycomparedtoyoungerpatientsinthe
Netherlands:stageatdiagnosis,treatmentandsurvivalin127,805unselectedpatients.BreastCancerRes
Treat2010124:801.
10. vandeWaterW,MarkopoulosC,vandeVeldeCJ,etal.Associationbetweenageatdiagnosisand
diseasespecificmortalityamongpostmenopausalwomenwithhormonereceptorpositivebreastcancer.
JAMA2012307:590.
11. NicholAM,YerushalmiR,TyldesleyS,etal.Acasematchstudycomparingunilateralwithsynchronous
bilateralbreastcanceroutcomes.JClinOncol201129:4763.
12. WeissenbacherTM,ZschageM,JanniW,etal.Multicentricandmultifocalversusunifocalbreastcancer:is
thetumornodemetastasisclassificationjustified?BreastCancerResTreat2010122:27.
13. LynchSP,LeiX,ChavezMacGregorM,etal.Multifocalityandmulticentricityinbreastcancerandsurvival
outcomes.AnnOncol201223:3063.
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14. SwainSM,JeongJH,GeyerCEJr,etal.Longertherapy,iatrogenicamenorrhea,andsurvivalinearly
breastcancer.NEnglJMed2010362:2053.
Topic737Version36.0

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GRAPHICS
Tumornodemetastases(TNM)stagingsystemforcarcinomaofthe
breast
Primarytumor(T)*
TX

Primarytumorcannotbeassessed

T0

Noevidenceofprimarytumor

Tis

Carcinomainsitu

Tis(DCIS)

Ductalcarcinomainsitu

Tis(LCIS)

Lobularcarcinomainsitu

Tis(Paget's)

Paget'sdisease(Pagetdisease)ofthenippleNOTassociatedwithinvasive
carcinomaand/orcarcinomainsitu(DCISand/orLCIS)intheunderlyingbreast
parenchyma.CarcinomasinthebreastparenchymaassociatedwithPaget's
diseasearecategorizedbasedonthesizeandcharacteristicsoftheparenchymal
disease,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)of
theskin,whichdonotmeetthecriteriaforinflammatorycarcinoma

T4c

BothT4aandT4b

T4d

Inflammatorycarcinoma

PosttreatmentypT.Theuseofneoadjuvanttherapydoesnotchangetheclinical
(pretreatment)stage.Clinical(pretreatment)Twillbedefinedbyclinicalandradiographicfindings,
whileypathologic(posttreatment)Twillbedeterminedbypathologicsizeandextension.TheypT
willbemeasuredasthelargestsinglefocusofinvasivetumor,withthemodifier"m"indicating
multiplefoci.Themeasurementofthelargesttumorfocusshouldnotincludeareasoffibrosis
withinthetumorbed.

Regionallymphnodes(N)
Clinical
NX

Regionallymphnodescannotbeassessed(eg,previouslyremoved)

N0

Noregionallymphnodemetastases

N1

MetastasestomovableipsilaterallevelI,IIaxillarylymphnode(s)

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N2

MetastasesinipsilaterallevelI,IIaxillarylymphnodesthatareclinicallyfixedor
mattedorinclinicallydetectedipsilateralinternalmammarynodesinthe
absenceofclinicallyevidentaxillarylymphnodemetastases
N2a

MetastasesinipsilaterallevelI,IIaxillarylymphnodesfixedtooneanother(matted)or
tootherstructures

N2b

Metastasesonlyinclinicallydetectedipsilateralinternalmammarynodesandinthe
absenceofclinicallyevidentlevelI,IIaxillarylymphnodemetastases

N3

Metastasesinipsilateralinfraclavicular(levelIIIaxillary)lymphnode(s)withor
withoutlevelI,IIaxillarylymphnodeinvolvementorinclinicallydetected
ipsilateralinternalmammarylymphnode(s)withclinicallyevidentlevelI,II
axillarylymphnodemetastasesormetastasesinipsilateralsupraclavicularlymph
node(s)withorwithoutaxillaryorinternalmammarylymphnodeinvolvement
N3a

Metastasesinipsilateralinfraclavicularlymphnode(s)

N3b

Metastasesinipsilateralinternalmammarylymphnode(s)andaxillarylymphnode(s)

N3c

Metastasesinipsilateralsupraclavicularlymphnode(s)

Pathologic(pN)**
pNX

Regionallymphnodescannotbeassessed(eg,previouslyremoved,ornot
removedforpathologicstudy)

pN0

Noregionallymphnodemetastasisidentifiedhistologically

pN0(i)

Noregionallymphnodemetastaseshistologically,negativeimmunohistochemistry
(IHC)

pN0(i+)

Malignantcellsinregionallymphnode(s)nogreaterthan0.2mm(detectedby
H&EorIHCincludingisolatedtumorcellclusters(ITC))

pN0(mol)

Noregionallymphnodemetastaseshistologically,negativemolecularfindings(RT
PCR)

pN0(mol+)

Positivemolecularfindings(RTPCR),butnoregionallymphnodemetastases
detectedbyhistologyorIHC

pN1

Micrometastasesormetastasesin13axillarylymphnodesand/orininternal
mammarynodeswithmetastasesdetectedbysentinellymphnodebiopsybutnot
clinicallydetected

pN1mi

Micrometastases(greaterthan0.2mmand/ormorethan200cells,butnonegreater
than2.0mm)

pN1a

Metastasesin13axillarylymphnodes,atleastonemetastasisgreaterthan2.0mm

pN1b

Metastasesininternalmammarynodeswithmicrometastasesormacrometastases
detectedbysentinellymphnodebiopsybutnotclinicallydetected

pN1c

Metastasesin13axillarylymphnodesandininternalmammarylymphnodeswith
micrometastasesormacrometastasesdetectedbysentinellymphnodebiopsybutnot
clinicallydetected

pN2

Metastasesin49axillarylymphnodesorinclinicallydetectedinternal
mammarylymphnodesintheabsenceofaxillarylymphnodemetastases

pN2a

Metastasesin49axillarylymphnodes(atleastonetumordepositgreaterthan2.0mm)

pN2b

Metastasesinclinicallydetectedinternalmammarylymphnodesintheabsenceof
axillarylymphnodemetastases

pN3

Metastasesintenormoreaxillarylymphnodesorininfraclavicular(levelIII

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axillary)lymphnodesorinclinicallydetectedipsilateralinternalmammary
lymphnodesinthepresenceofoneormorepositivelevelI,IIaxillarylymph
nodesorinmorethanthreeaxillarylymphnodesandininternalmammary
lymphnodeswithmicrometastasesormacrometastasesdetectedbysentinel
lymphnodebiopsybutnotclinicallydetectedorinipsilateralsupraclavicular
lymphnodes
pN3a

Metastasesintenormoreaxillarylymphnodes(atleastonetumordepositgreaterthan
2.0mm)ormetastasestotheinfraclavicular(levelIIIaxillarylymph)nodes

pN3b

Metastasesinclinicallydetectedipsilateralinternalmammarylymphnodesinthe
presenceofoneormorepositiveaxillarylymphnodesorinmorethanthreeaxillary
lymphnodesandininternalmammarylymphnodeswithmicrometastasesor
macrometastasesdetectedbysentinellymphnodebiopsybutnotclinicallydetected

pN3c

Metastasesinipsilateralsupraclavicularlymphnodes

PosttreatmentypN
Posttreatmentyp"N"shouldbeevaluatedasforclinical(pretreatment)"N"methodsabove.
Themodifier"sn"isusedonlyifasentinelnodeevaluationwasperformedaftertreatment.Ifno
subscriptisattached,itisassumedthattheaxillarynodalevaluationwasbyaxillarynode
dissection(AND).
TheXclassificationwillbeused(ypNX)ifnoypposttreatmentSNorANDwasperformed
NcategoriesarethesameasthoseforpN

Distantmetastasis(M)
M0

Noclinicalorradiographicevidenceofdistantmetastases

cM0(i+)

Noclinicalorradiographicevidenceofdistantmetastases,butdepositsof
molecularlyormicroscopicallydetectedtumorcellsincirculatingblood,bone
marrow,orothernonregionalnodaltissuethatarenolargerthan0.2mmina
patientwithoutsymptomsorsignsofmetastases

M1

Distantdetectablemetastasesasdeterminedbyclassicclinicalandradiographic
meansand/orhistologicallyprovenlargerthan0.2mm

PosttreatmentypMclassification.TheMcategoryforpatientstreatedwithneoadjuvant
therapyisthecategoryassignedintheclinicalstage,priortoinitiationofneoadjuvanttherapy.
Identificationofdistantmetastasesafterthestartoftherapyincaseswherepretherapyevaluation
showednometastasesisconsideredprogressionofdisease.Ifapatientwasdesignatedtohave
detectabledistantmetastases(M1)beforechemotherapy,thepatientwillbedesignatedasM1
throughout.

Anatomicstage/prognosticgroups
0

Tis

N0

M0

IA

T1

N0

M0

IB

T0

N1mi

M0

T1

N1mi

M0

T0

N1

M0

T1

N1

M0

T2

N0

M0

IIA

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IIB

T2

N1

M0

T3

N0

M0

T0

N2

M0

T1

N2

M0

T2

N2

M0

T3

N1

M0

T3

N2

M0

T4

N0

M0

T4

N1

M0

T4

N2

M0

IIIC

AnyT

N3

M0

IV

AnyT

AnyN

M1

IIIA

IIIB

*TheTclassificationoftheprimarytumoristhesameregardlessofwhetheritisbasedonclinicalor
pathologiccriteria,orboth.Designationshouldbemadewiththesubscript"c"or"p"modifiertoindicate
whethertheTclassificationwasdeterminedbyclinical(physicalexaminationorradiologic)orpathologic
measurements,respectively.Ingeneral,pathologicdeterminationshouldtakeprecedenceoverclinical
determinationofTsize.
Sizeshouldbemeasuredtothenearestmillimeter.Ifthetumorsizeisslightlylessthanorgreater
thanacutoffforagivenTclassification,itisrecommendedthatthesizeberoundedtothemillimeter
readingthatisclosesttothecutoff.
Multiplesimultaneousipsilateralprimarycarcinomasaredefinedasinfiltratingcarcinomasinthesame
breast,whicharegrosslyormacroscopicallydistinctandmeasurable.Tstageisbasedonlyonthelargest
tumor.Thepresenceandsizesofthesmallertumor(s)shouldberecordedusingthe"(m)"modifier.
InvasionofthedermisalonedoesnotqualifyasT4dimplingoftheskin,nippleretraction,orany
otherskinchangeexceptthosedescribedunderT4bandT4dmayoccurinT1,T2,orT3without
changingtheclassification.Thechestwallincludesribs,intercostalmuscles,andserratusanterior
muscle,butnotthepectoralismuscles.
Inflammatorycarcinomaisaclinicalpathologicentitycharacterizedbydiffuseerythemaandedema
(peaud'orange)involvingathirdormoreoftheskinofthebreast.Theseskinchangesaredueto
lymphedemacausedbytumoremboliwithindermallymphatics.Althoughdermallymphaticinvolvement
supportsthediagnosisofinflammatorybreastcancer,itisneithernecessarynorsufficient,inthe
absenceofclassicalclinicalfindings,forthediagnosisofinflammatorybreastcancer.
Ifacancerwasdesignatedasinflammatorybeforeneoadjuvantchemotherapy,thepatientwillbe
designatedtohaveinflammatorybreastcancerthroughout,evenifthepatienthascompleteresolution
ofinflammatoryfindings.
Clinicallydetectedisdefinedasdetectingbyimagingstudies(excludinglymphoscintigraphy)orby
clinicalexaminationandhavingcharacteristicshighlysuspiciousformalignancyorapresumedpathologic
macrometastasisbasedonfineneedleaspirationbiopsywithcytologicexamination.Confirmationof
clinicallydetectedmetastaticdiseasebyfineneedleaspirationwithoutexcisionbiopsyisdesignatedwith
an(f)suffix,forexample,cN3a(f).Excisionalbiopsyofalymphnodeorbiopsyofasentinelnode,inthe
absenceofassignmentofapT,isclassifiedasaclinicalN,forexample,cN1.Informationregardingthe
confirmationofthenodalstatuswillbedesignatedinsitespecificfactorsasclinical,fineneedleaspiration,
corebiopsy,orsentinellymphnodebiopsy.Pathologicclassification(pN)isusedforexcisionorsentinel
lymphnodebiopsyonlyinconjunctionwithapathologicTassignment.
Classificationisbasedonaxillarylymphnodedissectionwithorwithoutsentinellymphnodebiopsy.
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Classificationbasedsolelyonsentinellymphnodebiopsywithoutsubsequentaxillarylymphnode
dissectionisdesignated(sn)for"sentinelnode,"forexample,pN0(sn).
**Isolatedtumorcellclusters(ITC)aredefinedassmallclustersofcellsnotgreaterthan0.2mm,or
singletumorcells,oraclusteroffewerthan200cellsinasinglehistologiccrosssection.ITCsmaybe
detectedbyroutinehistologyorbyimmunohistochemical(IHC)methods.NodescontainingonlyITCsare
excludedfromthetotalpositivenodecountforpurposesofNclassificationbutshouldbeincludedinthe
totalnumberofnodesevaluated.
RTPCR:reversetranscriptase/polymerasechainreaction.
"Notclinicallydetected"isdefinedasnotdetectedbyimagingstudies(excludinglymphoscintigraphy)
ornotdetectedbyclinicalexamination.
"Clinicallydetected"isdefinedasdetectedbyimagingstudies(excludinglymphoscintigraphy)orby
clinicalexaminationandhavingcharacteristicshighlysuspiciousformalignancyorapresumedpathologic
macrometastasisbasedonfineneedleaspirationbiopsywithcytologicexamination.
Anatomicstage:
M0includesM0(i+).
ThedesignationpM0isnotvalidanyM0shouldbeclinical.
IfapatientpresentswithM1priortoneoadjuvantsystemictherapy,thestageisconsideredStageIV
andremainsStageIVregardlessofresponsetoneoadjuvanttherapy.
Stagedesignationmaybechangedifpostsurgicalimagingstudiesrevealthepresenceofdistant
metastases,providedthatthestudiesarecarriedoutwithin4monthsofdiagnosisintheabsenceof
diseaseprogressionandprovidedthatthepatienthasnotreceivedneoadjuvanttherapy.
Postneoadjuvanttherapyisdesignatedwiththe"y"prefix.Forpatientswithapathologiccomplete
response(pCR)toneoadjuvanttherapy,nostagegroupisassigned(ie,yT0N0M0).
T1includesT1mi.
T0andT1tumorswithnodalmicrometastasesonlyareexcludedfromStageIIAandareclassified
StageIB.
UsedwiththepermissionoftheAmericanJointCommitteeonCancer(AJCC),Chicago,Illinois.The
originalsourceforthismaterialistheAJCCCancerStagingManual,SeventhEdition(2010)publishedby
SpringerNewYork,Inc.
Graphic65393Version10.0

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Disclosures
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,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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