Developing evidence-based measures of care for breast cancer

210 Pages·1999·6.7 MB·English

by  Pearson, Marjorie L

DevelopingEvidence-Based
MeasuresofCareforBreast
Cancer
MarjorieL.Pearson, VirginiaErickson,
JohnAdams,KatherineL.Kahn
January1-f.1999
PreparedfortheHealthCareFinancing
Administration
1 1
TABLEOFCONTENTS
Page
Methods 2..
PublishedPracticeGuidelines 3.
ProposedProcessMeasures 4.
Process-OutcomeResearch 4.
Domain1: RecognitionandDiagnosisoftheBreastProblem,SeverityAssessment,andReferral 3
Domain2: InitialSurgicalTreatment 4
TypeofSurgery 4
UseofEstrogenReceptorstoDetermineOptimalTherapy 5
.ClearSurgicalMargins 5
UseofAxillaryNodeDissection 5
Domain3: PatientChoiceofTreatment 6
Domain4: RadiotherapyTreatments 7
Domain5: ChemotherapyTreatments 7
Domain6; TamoxifenTreatments 8
Domain7: CareFollowingInitialSurgery/Radiotherapy 9
Domain8: TreatmentofMorbidandComorbidSymptoms,Signs,andConditions 9
Conclusion IQ
References 133
Tables
Table1 BreastCancerLiteratureSearch: SummaryofSearches 1
Table2 PublishedBreastCancerGuidelines 1.3
Table3 PublishedBreastCancerGuidelines-Domain1 16
Table4 PublishedBreastCancerGuidelines-Domain2 36
Table5 PublishedBreastCancerGuidelines-Domain3 53
Table6 PublishedBreastCancerGuidelines-Domain4 65
Table7 PublishedBreastCancerGuidelines-Domain5 75
Table8 PublishedBreastCancerGuidelines-Domain6 87
Table9 PublishedBreastCancerGuidelines-Domain7 96
Table10 PublishedBreastCancerGuidelines-Domain8 106
Table1 RecommendedMeasures 1.11
Table12 ProposedMeasureSetsbyDomain-Domain1 112
Table13 ProposedMeasureSetsbyDomain-Domain2 116
Table14 ProposedMeasureSetsbyDomain-Domain3 120
Table15 ProposedMeasureSetsbyDomain-Domain4 122
Table16 ProposedMeasureSetsbyDomain-Domain5 124
Table17 ProposedMeasureSetsbyDomain-Domain6 126
Table18 ProposedMeasureSetsbyDomain-Domain7 128
Table19 ProposedMeasureSetsbyDomain-Domain8 130
Table20 SummaryofQualityofLife/PsychosocialOutcomesforBreastConserving
SurgeryVersusMastectomy 132
^i
DEVELOPINGEVIDENCE-BASEDMEASURESOFCAREFORBREASTCANCER
Asourhealthcaresystemhasincreasinglymovedtowardsacompetitivemarketmodel, •
pressureshavemountedformoreandbetterinformationonthequalityofhealthservices.
Healthservicesresearchersareinterfacingwithcorporateexecutives,healthcare
administrators,andclinicianstomoldstrategiesandtechniquesformeasuringprovider
performancetoproduceaccurateinformationthatallpartiescanconfidentlyuseintheirdecision
making. Developingmeaningfulmeasuresofqualityperformanceisoneofthefirstchallenges
faced.
Performancemeasurementinvolvesbothassessingthequalityofthecaredeliveredbya
providerandrepresentingthatqualityassessmentintermssuitableforfaircompansonwith
otherproviders. AccordingtotheInstituteofMedicine(iOM),thequalityofcareis"thedegree
towhichhealthservicesforindividualsandpopulationsincreasethelikelihoodofdesiredhealth
outcomesandareconsistentwithcurrentprofessionalknowledge."^ Tomeasureperformance,
onemustcollectandassesscomparableinformationonthequalityofthecaredeliveredby
specifichealthcareproviders. Performancecanbemeasuredattheleveloftheindividual,e.g.,
physician,ortheorganization,e.g.,healthcareplan,hospital,medicalgroup,specialty,or
geographicarea. Thefindingsarethencomparedtothoseofotherindividualsorgroupsortoa
benchmarksuchasagoalorstandard.
Mammographyscreeningisafrequentfocusofperformancemeasurement. TheHEDIS3.0
reportingsetmeasurerelatedtobreastcancer,forexample,istherateofmammography
screeningamongwomenaged52through69.^ Breastcancerismulti-faceted,however,and
performancemeasurementispossibleacrossawholespectrumofcare. Inthispaper,wefocus
onevidencedefiningqualityofthecarewhichfollowsanabnormalfindingonamammogramor
physicalexam.
Performancemeasurescanreportontheprocessesofcare,whatphysiciansandnursesdoto
patients,aswellastheoutcomesofthecareexperiencedbythepatient.^" Forexample,the
rateofradiationtherapyamongpatientstreatedwithbreastconservingsurgerydefinesa
processmeasure,whilepatient-reportedwellbeingandsatisfactionareexamplesofoutcome
measures. AssuggestedbytheIOMdefinitionofquality,performancemeasuresshouldbe
supportedbyscientificallysoundresearchdemonstratingthatbetterperformanceofthe
processesisassociatedwithimprovedoutcomesforpatientswithbreastcancer. Inmany
cases,performancemeasuresarederivedfrompracticeguidelineswhich,inturn,werebased
onscientificevidenceandexpertjudgment. Todevelopmeaningfulperformancemeasures,one
mustidentifythepracticeguidelinesandunderlyingbodyofscientificevidenceacrossthe
spectrumofbreastcancercare. Thepurposeofthispaperistoprovideanoverviewofthe
existingpracticeguidelinesandevidenceshowingwhichprocessesofbreastcancercarelead
todesiredpatientoutcomes.
METHODS '
Toidentifybreastcancerpracticeguidelinesandrecommendedprocessmeasures,we
searchedtheMEDLINEdatabaseforEnglish-languagearticlespublishedduringorafter1990
onthesubjectofbreastneoplasmsandthetitleword"consensus"orkeyword"clinicalpractice
guidelines." Wesupplementedthiswithasearchofthe1993topresentdatabaseonthesubject
ofbreastneoplasmsandanyofthefollowing, a)keyword"performancemeasurement;"b)
subject"healthservicesresearch;"andc)subject"qualityofhealthcare;"andd)keyword
"qualityindicators." Wealsoscreenedreferencesinknownliteratureonthesubjectand ' -
conductedadditionalsearchesoftheHealthStar,Cancerlit,andEnnbasedatabases.
Toidentifyevidenceoflinkagesbetweenprocessesandoutcomesofbreastcancercare,we
searchedthecomputerizedbibliographicdatabaseMEDLINEforEnglish-languagearticles
publishedduringthelastfiveyears(1993topresent)reportingresultsofstudiesanalyzingthe
relationshipbetweenanyofanumberofprocessesandoutcomes. Table1showsthesearch
topics,specificsubjectheadingsandkeywords,andthenumberofcitationsidentified. The
citationtitles,andinmanycasestheabstracts,werereviewedbytheresearchersfordata-
basedfindingsonanyrelationshipbetweenaspecifiedprocessandpatientoutcomes. Wehave
notassessedthequalityoftheevidenceitself.
Weareinterestedinprocessesofbreastcancercareapplicabletothediagnosisandthefirst -
yearofcareforelderlypatientsdiagnosedwithearlystagebreastcancer. Ourconceptual
frameworkviewsthespectrumofprocessesintermsofeightdomainsofrecognitionand
diagnosis,initialsurgicaltreatment,patientchoiceoftreatment,radiotherapytreatments,
chemotherapytreatments,tamoxifenorotheradjuvanttreatments,carefollowinginitial
surgery/radiotherapy,andtreatmentofmorbidandcomorbidsymptoms,signs,andconditions.
PUBLISHEDPRACTICEGUIDELINES
AccordingtotheInstituteofMedicine(lOM)definition,practiceguidelinesare"systematically
developedstatementstoassistpractitionerandpatientdecisionsaboutappropriatehealthcare
forspecificclinicalcircumstances."^ Performancemeasures,ontheotherhand,aredeveloped
astoolsforevaluatingconformitytopracticeguidelines. Knowledgeoftheprevailingpractice
guidelinesisthereforecriticaltoperformancemeasurementdevelopment.
Anumberoforganizationsfromaroundtheworldhaveundi;er*tJak'e-'nmajoreffo.rVt's.t.odevelop ' .
evidence-basedprocessguidelinesorrecommendations. Thesearchmethoddescribedabove
located23publishedaccountsofpracticeguidelines(after1990)forearlystagebreastcancer
care. TheseguidelineeffortsarelistedonTable2(startingwiththosemostrecent),alongwith
indicatorsofthedomainsofcareaddressedbyeach. Theyrangefrominternationaleffortssuch
astheInternationalConferenceonAdjuvantTherapyofPrimaryBreastCancerTreatmentto
national-leveleffortsintheUnitedStates,England,Australia,andelsewheretoprovider-level
guidelinessuchasthoseoftheTexasOncologyP.A. Includedamongthesponsorsofthe
UnitedStateseffortsaretheNationalCancerInstitute(NCI),theNationalInstitutesofHealth
(NIH),theAmencanSocietyofClinicalOncology(ASCO),theNationalComprehensiveCancer
Network(NCCN),theAmericanCollegeofRadiologists(ACR),theAmericanCollegeof
Surgeons,CollegeofAmericanPathologists(CAP),andtheSocietyofSurgicalOncology - •
(SSO).
Someguidelinesetsfocusspecificallyononedomainofcaretoearlystagebreastcancer
patients,oreventooneprocessareawithinadomain. Anexamplearetherecommendations
onfineneedleaspiration(FNA)biopsyputforthbytheNationalCancerInstitutesponsored
conferencein1996.® Otherguidelinesetscovermultipledomains. Thepracticeguidelines
publishedbytheCanadianMedicalAssociation(CMA),theNationalHealthServiceExecutive
InitiativeinGreatBritain(NHS),theBritishAssociationofSurgicalOncology,andtheNational
HealthandMedicalResearchCouncilinAustralia,forexample,includerecommendationsinall
eightdomainsofcare. •:> ,,' -. • , , -•
Tables3through10presentthespecificrecommendationsbydomain. Eachtablegivesall
guidelinespertainingtothatdomainofcare. Guidelineswhichaddressmorethanonedomain
(e.g.,acombinationofchemotherapyandtamoxifen)arerepeatedundereachrelevantdomain.
SSprii)-- ''^'%!^,fi-5
Theguidelineformatsvarysomewhatamongthedifferentorganizations. Mostweredeveloped
astsrurcetcuoremmreencdoamtmieonndsatfoironprsovaisdewerllp.roWceessle,fbtutthessoemelatsteertstyipnecsluidneoeuvritdaebnlceessbteactaeumseentwseorwished
toaccuratelyreflectthefullspectrumoftheguidelinesetandbecausetheevidenceand
structuralstatementshavedirectimplicationsforprocess.
PROPOSEDPROCESSMEASURES ' -
Someorganizationsandresearchteamshaveproposed,andinsomecasesimplemented,
performancemeasuresets. Table11illustratesthevarietyofmeasureproponentsandthe
domainsinwhichtheirmeasuresapply. Tables12-19presentthesemeasuresbythedomain
addressed. Aswiththeguidelines,theformatsusedbythedifferentgroupsvary.
PROCESS-OUTCOMERESEARCH
Theextentofthedocumentationofrelationshipsbetweenprocessesofcareandlong-term
outcomesvariesacrossandwithindomainsofcare. Notallaspectsofbreastcancercarethat
arebelievedtobeassociatedwithimprovedoutcomeshavebeendocumentedwithaprocess-
outcomelinkintheelderly. Wheredataregardingtheelderlyareavailable,wehave
documentedthem. However,wedonotbelieveaqualityofcaremodelforMedicarepatients
wouldbecompleteifitdidnotsupplementrandomizedcontroltrialdataspecificallyassessing
effectivenessintheelderlywithotherclinicallyimportantdata.
Relevantoutcomesforbreastcancerpatientsincludesurvival,recurrence,patientsatisfaction,
shortandlong-termfunctionalstatusandqualityoflife. Inthefollowingsectionsweprovidea
briefoverviewofexistingevidenceforprocess-outcomerelationshipswithintheeightdomainsof
care.
Domain1: RecognitionandDiagnosisoftheBreastProblem,SeverityAssessment,and
Referral
Earlydetectionofbreastcancerisassociatedwithearlierstageofdiagnosisaswellasearlier
treatmentinterventions.'^ Bothearlystageatdiagnosisandearlyinterventionareassociated .
withimprovedpatientoutcomes. Asatisfactoryexperienceforthepatientatthetimeof
diagnosisisusefulforassuringpatientcomplianceaswellasforencouragingpatient
compliancewithfuturebreastcancerassociatedinterventions. Severalstudieshavedescribed
theangstofwomenwhoseinitialdiagnosticwork-upisincorporatedintosurgicaltreatmentwith
mastectomy. Womenwhohavetimetoprocessthediagnosisofbreastcancerpriorto
undergoingmastectomyhavebetterpsychosocialoutcomes.^^^°
Domain2: InitialSurgicalTreatment
TypeofSurgery
Theliteratureclearlydocumentssimilarsurvivaloutcomesforwomenwithearlystagebreast
cancertreatedwithmastectomyascomparedwithbreastconservingsurgery. Sixlarge
prospectiverandomizedtrialshaveassessedmortalityandrecurrencefollowingmastectomyas
comparedwithbreastconservingsurgery.^^"^^ TheearlieststudyfromtheNationalCancer
InstituteinMilan,Italyshowedafteraminimumof10yearsoffollow-upnodetecteddifferences
inrelapse-freeoroverallsurvivalratesforeithernodenegativeornodepositivewomen.^^ The
NationalSurgicalAdjuvantBreastandBowelProject(NSABP-B-06)randomizedwomentoa
three-armtrialcomparingmastectomywithlumpectomywithoutradiotherapyandtolumpectomy
withradiotherapy. Aftermorethaneightyearsoffollow-upnodifferencesindistantdisease-free
survivaloroverallsurvivalrateshavebeennotedbetweenwomenwithmastectomyandwomen
withlumpectomywithorwithoutradiotherapy.^" Theuseofradiotherapywasnotassociated
withimprovementsinsurvivalbutwasassociatedwithasignificantreductionintheincidenceof
localrecurrenceofthebreast. Theprobabilityofarecurrenceinthebreastwas12%for
patientswithradiotherapyascomparedto42%forpatientswithoutradiotherapy. Theimproved
recurrenceratewithradiotherapywasnotedregardlessofnodalstatus,tumorsize,andpatient
age.
Similarfindingsofequivalentoutcomes(survivalandrecurrence)havebeennotedbystudiesof
theEuropeanOrganizationforResearchandTreatmentofCancer(EORTC),^^theDanish
BreastCancerCooperativeGroupTrial,^^andtheNationalCancerInstituteEarlyBreastCancer
Triaf^whichcomparemastectomywithbreastconservingtherapy. Harrishasemphasized
recurrenceastheproblemfollowingbreast-conservingtreatmentwithrecurrenceratesvarying
at8-10yearsbetween4%and20%followingbreastconservingtreatments(withradiotherapy)
ascomparedwithratesofrecurrenceof2%to9%followingmastectomy.^®
Analysisofpsychologicaladjustmentandqualityoflifeaftersurgeryfoundnosignificant
differencesinmood,adjustment,qualityoflife,andfunctionalstatusbetweenpatientswith
breastconservingsurgeryversusmastectomy.^^^° However,researchersfoundthat
mastectomypatientsreportedmorebodyimageandclothingproblems. Thisdifferencedidnot
appeartoaffectmoodorqualityoflife. Therewasalsosomesuggestionthattheaddedburden
forbreastconservingsurgeryofradiationtherapymayslowmoodrecoveryduringtheearly
post-surgicalperiod.^""''^°°'*""''''"°""'"""'' Table20summarizestheevidenceregarding
psychosocial/qualityoflifeoutcomesforbreastconservingsurgeryversusmastectomy.
UseofEstrogenReceptorstoDetermineOptimalTherapy
Duringtheearly1980ssubstantialprogresswasmaderegardingtheuseofestrogenreceptors
topredicttheresponsivenessofbreastcancertohormonalinterventions. Somehave
advocatedtheuseoftamoxifenasadjuvanttherapyforallpostmenopausalwomenmakingthe
needtoobtainestrogenreceptorslessimportant. However,evenifoneweretoarguethatall
postmenopausalwomenshouldgetadjuvanthormonalintervention,thenbenefitsfromknowing
estrogenreceptorstatusatthetimeofdiagnosiswouldstillbeapparentforwomenwith
recurrencesinceinitialestrogenreceptorstatuswouldbeusefulinplanningtherapyatthetime
ofrecurrence.^^ Accordingly,assessmentofestrogenreceptorsatthetimeofdiagnosisshould
beobtained.
ClearSurgicalMargins ''
Clearsurgicalmarginsremainoneofthemostimportantpredictorsofrecurrence. Multiple
studieshaveshownthatclearsurgicalmarginspredictlessrecurrence.'^-" Accordingly,where
possibleclearmarginsshouldbeobtainedanddecisionsregardingradiationtherapyshouldbe
influencedbymarginstatus.
UseofAxillaryNodeDissection • .> , . > . .-
Historically,axillarylymphnodedissectionhasbeenrecommendedtoassistinthe
prognosticationofbreastcancerpatients. Duringthedecadeswhentreatmentdefinitively
dependedupontheextentoflymphnodeinvolvement,axillarylymphnodedissectionbecamea
standardcomponentoftheprotocolofmanysurgeonscaringforbreastcancer. Withtime,two
newlinesofevidencehavesuggestedthattheuseoflymphnodedissectionshouldbeapplied
^^*H' '';^^'i^M
onlytosubsetsofwomen. -n. ^ op'^r^ - ' - .; /, . . ,
First,theconductofaxillarylymphnodedissectionhasbeenassociatedwithadditionalshort
andintermediatetermmorbidityforwomen. Mostnotably,patientswhoreceiveaxillarynode
dissectionand/orradiationforbreastcancerareatriskforthedevelopmentoflymphedema,and
otherarmmorbiditiessuchaspain,paresthesias,weaknessandimpairedshoulderfunction.
Regardlessofthetypeofmastectomy,womenwhohadundergoneaxillarydissectionhad
significantlymorearmproblems(24%-64%)thanthosewithoutaxillarydissection(0%-33%).^''
Thereportedincidenceoflymphedemafollowingbreastcancertherapyvarieswidely,Kissin
reportsalymphedemarateof25%overallandarateof38%forthosepatientsreceivingaxillary
nodedissectionandradiationtherapy.^^
Withtheawarenessofthisadditionalmorbiditytheroutineuseofaxillarylymphnodeforall
womenhasbeenquestioned. Infact,forthesubsetofwomenwithinsitudisease,ithasbeen
recommendedthataxillarylymphnodedissectionshouldbeavoidedbecausewomenwith
axillarylymphnodedissectionsufferworseoutcomesasaresultofarmmorbidity.^^ Snipeshas
foundthatamongwomenreceivingbreastconservingsurgery,lymphnodedissectionwas
performedon15%ofwomenwithinsitutumors.^'™''^°°'""'"^"°*"*""*"
Second,ithasbecomeapparentthatformanywomen,particularlyolderwomen,treatmentswill
notchangedependinguponhistologicnodalstatus. TheNSABPB-20trialdemonstratedthat
chemotherapyandtamoxifenprovidedimprovedoutcomes(i.e.,diseasefreesurvival)forall
breastcancerwomenwithnoparticularsubsetsbeingapparentwhowouldnotbenefitfrom
thesetreatments. Accordingly,thisstudychallengedthebasisforapplyingaxillarylymphnode
dissectiontoallwomenwithanewdiagnosisofbreastcancer. Infact,amajorconclusionofthis
trialwasthataxillarystagingwasnotanabsoluterequirementformedicaldecisionsregarding
adjuvanttherapy,althoughknowledgeofaxillarylymphnodestatusanditseffectonprognosis
mighthelpsomepatientstocometoamoreinformeddecisionregardingtheneedforsystemic
therapy.^'' Haffty^®hasadditionallydemonstratednobenefittooutcomesforsubsetsofwomen
withaxillarylymphnodedissection. Accordingly,severalgroupshaveadvocatedinforming
womenwhoarenotlikelytobenefitfromaxillarynodedissectionofoutcomeswithascompared
towithoutaxillarynodedissectionsothatwomenwillbeinformed,inadvanceofthesurgery,of
theextentandexpectedmorbidityofthesurgery.^'™''^ooKmarknotdefined.,29.30 |_|afftynotedthatthe
vastmajority(95%)ofMedicarewomenpresentingwithanewdiagnosisofnonpalpablebreast
cancerhadnode-negativedisease.^™''Bookmarknotdefined. ^jgexpectedthatwithincreasinguseof
mammographythatthehighpercentageofpatientswithhistologicallylymphnodenegative
diseasewillincrease. Forexample,atYaletheproportionofwomenwithnegativenodesafter
conservativetreatmentandaxillarylymphnodedissection increasedfrom70%in1989to82%
between1992and1995, EvenforthesubsetofMedicarewomenwithnodepositivedisease,
thelikelihoodthatnodalstatuswouldchangetherapyisevenlower.^"°''^°°'"""''"°*''*""^'' Thisis
especiallytrueasmoreevidencemountssuggestingwomen,especiallypostmenopausal
women,haveimprovedoutcomeswithadjuvanttherapyregardlessofnodalstatus. Thisistrue
fortheuseofbothtamoxifenandalsofortheuseofchemotherapy.^""''°°°'""'^"°"""""'-
Domains: PatientChoiceofTreatment
Outcomesfollowingsurgeryforearlystagebreastcancervaryasafunctionofpatientchoiceas
wellasafunctionoftypeofsurgery. Choiceindecision-makingforbreastcancertherapyhas
beenshowntobeassociatedwithincreasedphysicalandfunctionalwell-beingatoneyear,^^
decreasedanxietyanddepressionatthreemonths,^^^^decreasedanxietyanddepressionat
threeyearfollow-up,^"andhigherlifesatisfactionatthreemonths.^^ Patientsnotoffereda
choiceoftherapywerefoundtohavehigherlevelsofanxietyanddepressionpreoperativelyand
foruptotwomonthspost-operativelyincomparisonwithpatientsofferedachoiceof
thpr^^nu^rror!Bookmarknotdefined.
Substantialresearchhasdocumentedthevalueofchoiceandinformationforpatientsingeneral
andforbreastcancerpatientsinparticular.^''°''^°°''"'"'<"°"''''"*''^^ Despitethis,someevidence
hasshownthatthepreferenceforanactiveoracollaborativeroleintreatmentdecision-making
declineswithage. Theelderlyaremorelikelytochooseapassiveornon-participatoryrolein
treatmentdecision-making.^''^^ Thereisnot,however,alinearrelationshipbetweenthe
perceivedneedforinformationabouttherapyoptionsandthedesiredparticipationindecision-
making. Morepatientswanttohaveinformationaboutdiagnosis,therapeuticoptions,andside
effects (90-92%)thanchooseparticipationinthetherapeuticdecision(25-69%).^™''^°°"""''"°*
deflned.-39
Whengivenachoice,between35-87%ofwomenelectbreastconservingsurgeryover
mastectomy.^™''^°°'""'"'"°"'*""*''-''°'''^ Whencomparedwithyoungerwomen,moreolderwomen
havetendedtochoosemastectomy,^'™''^°°'""''^"°"'"'"'''''^althougharecentstudyfoundthat
87%ofwomen70yearsofageandolderchosebreastconservingsurgery."^
Domain4: RadiotherapyTreatments
AsnotedaboveinDomain2,theNSABPstudiedbreastconservingsurgerywithascompared
towithouttheuseofradiotherapy. After12yearsoffollow-up,nodifferencewasfoundinoverall
survival,diseasefreesurvival,orsurvivalfreeofdiseaseatdistantsitesbetweenwomenwith
mastectomy,withlumpectomywithradiotherapyandlumpectomywithoutradiotherapy.'*''
Recurrencerateswerehigher(35%)forwomenwithlumpectomywithoutradiationascompared
to10%forwomenwithlumpectomywithradiation. ASwedishtrialalsofoundhigherrecurrence
ratesof20%versus3%forwomenwithoutascomparedtowithradiotherapy."^
Elderlywomenundergoingtherapyforbreastcancerreceiveradiationtherapyatlowerrates
thandotheiryoungercounterparts. Studieshaveshownthatageisanindependentpredictorof
receiptofradiationtherapyforbreastcancer,evenafteradjustmentforcomorbidity."^"'' Women
80yearsandolderwere90%lesslikelytoreceiveradiationtherapythanthoseyoungerthan
70."^ Frequencyofradiationtherapyalsodeclinesasafunctionofcomorbidity-from58%for
patientswithnocomorbiditiesto28%forpatientswith2ormorecomorbidconditions(Charlson
score).^™"Bookmarknotdefined, patjentcompllancewithradiationtherapyrecommendations
(completion)hasbeenreportedat94%.^"°"Bookmarknotdenned. .,:-
f
Domains: ChemotherapyTreatments ij .
Duringthe1980sitbecameapparentthatasignificantreductioninmortalitycouldbegainedfor
womenaged50yearsorolderwhoreceivedadjuvanttamoxifen."^ In1985,theNational
InstitutesofHealthConsensusConferenceadvocatedtamoxifenasthestandardtreatmentof
choiceforpostmenopausalwomenwithestrogenreceptor(ER)positivetumors.^° The
extensiveoverviewmeta-analysisinOxfordin1990^^comprisingmoreclinicaltrialsthanever
beforeindicatedthattamoxifencouldbenefitmostpatientswithprimarybreastcancerandthat
therewasalsoasignificantsurvivalbenefitforpatientswithnegativeaxillarylymphnodeswho
receivedadjuvantcombinationtherapy.^'™"^°°'"""'''"°"'*""*'' Themagnitudeofthissurvival
obnenleyfiatbofuortc4h%emaott1h0eryaepayrsafpoprepaarteidenttosbwiethsmnalelg,atwiivtehaaxnillaabrsyolluytmephodndosderse.ductioninmortalityof
In1982,theNationalSurgicalAdjuvantBreastandBowelProject(NSABP)initiatedaclinical
-^*^- '^i^^^
trial{B-14)withadjuvanttamoxifengiventopatientswithlymphnode-negative,ER-positive
primarybreastcancers. Analysisin1989"showedthattherewasasignificantreductionin
relapseratesforthewomenusingtamoxifen,althoughthesurvivalbenefitdidnotreach
statisticalsignificance. Theinvestigatorsconcludedthat,althoughtheprognosisforthese
cpaotmibeinntastoinontacmhoemxoitfheenrawpays.^g^o"o'd',eoaodKdmairtkinoontadlefibneedn,efjihtermeifgohrte,beaancehwietvrieadl,bNyStAhBePadBdi-t2i0o,nwoafs •>
initiatedwhichcomparedtamoxifenalonewithtamoxifenplusCMForMF(Cytoxan,
methotrexate,or5fluorouracil)chemotherapyinpatientswithaxillarylymphnode-negative,ER-
positivephmarybreastcancer. Theresultsfromthistrialshowthattheadditionof
chemotherapytotamoxifencausedafurtherimprovementindisease-freesurvivalofabout5%
andanadditionalimprovementinsurvivalofabout30/0ErronBookmarknotdenned, j^ggeresultswere
strikinglysimilartotheresultsfromthe1990overview"whichindirectlycomparedtamoxifen
alonewithtamoxifenpluspolychemotherapy.Thisworkshowednoeasilydiscerniblegroup
(age,menopausalstatus,andprimarytumorsize)wasidentifiedthatdidnotgainbenefit. This
beneficialeffectofaddingchemotherapytotamoxifeninpatientswithaxillarylymphnode-
negativeprimarybreastcancerisinkeepingwiththe1990overviewmeta-analysisdata^'™''
Bookmarknotdefined,^^^^y^indicatedthattheabsolutebenefitforadjuvantchemotherapywassimilar
forpatientswithlymphnode-negativeorlymphnode-positivebreastcancer. Thisfindingisnot
surprising,sinceaxillarylymphnodestatushasneverbeenshowntopredicttheefficacyof
adjuvantchemotherapyinimprovingoutcomes. Thereisnobiologicbasistosupposethat
axillarylymphnodeinvolvementshouldindicatechemosensitivity,andtherearereasonsto
supposethatlessextensivediseasemightbemorelikelytorespondtochemotherapy.^"°"
Bookmarknotdefined.
ThephncipalconclusionfromtheNSABPB-20trial^"'"'^""'""''*"""**''"*''-inconjunctionwiththe
datafromtheoverviewmeta-analysis,^™'''^°°'""'"*"°*"*"""*•isthatadjuvantchemotherapywillgive
risetosmallbutdefinitereductionsinrelapseanddeathinallsubgroupsofpatientscategorized
accordingtotumorsize,axillarylymphnodestatus,hormonereceptorstatus,age,and
menopausalstatus. Noeasilyidentifiedsubgroupofpatientsareapparentasthesolerecipients
ofthebenefitofadjuvantchemotherapywhomightbeselectedfortreatment. Accordingly,
Fisher,etalrecommendedthatonlythosepatientswithnoninvasivecancersand,perhaps,
thosewithverysmallscreen-detectedcancersshouldbeabsolutelyexcludedfrom
considerationofadjuvantchemotherapy.^'™''°°°'"""''"°"'**'""^
Althoughthisperspectivehasnotyet disseminatedintomanypracticesettings,itisexpected
thatitwillwithinthenextfewyearsasmoremethodsforminimizingthetoxicitiesof
chemotherapyareappliedtotheelderly. Slevinetal.^"notedthatmostpatientswithbreast
cancerwouldacceptseveretoxicityfromtreatmentinordertoachieveaslittleasa1%
improvementinsurvival. Powles^'™"^"""""'"""*"*""•"•notedthetoxicityfromadjuvant
chemotherapyisgenerallymildandseldomlifethreatening: therefore,a4%reductionin
mortalityat10yearsislikelytobeconsideredanattractiveoptionbymostpatientswithaxillary
lymphnode-negativeprimarybreastcancer.
Domain6: TamoxifenTreatments
TheEarlyBreastCancerTrialists'CollaborativeGroup^'""^""""""'''"""'*''"*''studiedwithmeta-
analysismorethan30,000womenrandomizedbetweentreatmentandcontrolfor
polychemotherapyandhormonaltherapy. Theyconcludedthatforwomenoveraged50and
specificallyforwomenoveraged70thattamoxifenhasbeenextensivelytestedandproduced
significantriskreductions. Forwomen70ormoreyearstheriskreductioninrecurrencewas
28%andinmortalitywas21%. Ifrestrictedtotrialsofatleasttwoormoreyearsriskreductions
forwomen70yearsormoreinrecurrencewasgreaterat33%andinmortalitywasgreaterat
25%. - • ,v. -
Aftertherecognitionthatpost-surgicaltreatmentwithtamoxifenimprovedoverallsurvivalamong
patientswithearlystagebreastcancer,evaluationswereinitiatedtounderstandtheoptimal
durationofsuchtreatments. TheSwedishBreastCancerCooperativeGrouprandomized
postmenopausalwomenwithearlystagebreastcancertoatrialoftwoversusfiveyearsof
adjuvanttamoxifentherapyduringthe1980s. Dailydoseswereeither20mg(twocenters)or40
mg(attheremainingthreecenters). Patientsassignedtoreceivefiveyearsoftamoxifen,
comparedwithtwoyearsoftamoxifenhadstatisticallysignificantimprovementsinevent-free
survivalwitharelativehazardof0.82(CI 0.71-0.96)andoverallsurvivalwitharelativehazard
of0.82(CI 0.69-0.99). Thesefindingstranslateintoan18%relativereductioninbothfirst
eventsandmortalitywiththelongertreatment. Thebenefitassociatedwiththelongertreatment
extendedtowomenregardlessoflymphnodestatus,butappearedtoberestrictedtowomen
whosetumorswereestrogenreceptorpositive.^^ TheOxfordmeta-analysisof133multinational
trialsshowedlongertermtamoxifen(atleasttwoyears)issignificantlymoreeffectivethan
shortertamoxifenregimentswithanoddsreductionof22%(p=.004). Thismeta-analysis
showedthatforwomenover50years,tamoxifenproducedsignificantbenefits,evenamong
estrogenreceptornegativewomenwitharecurrencereductionof16%(p=.001)andamortality
reductionof16%(p=.004). Fisher,^^additionallyshowedasubstantialsurvivalbenefittowomen
aged50orgreaterforwomenusingtamoxifenforfiveyearsascomparedwithalongerpenod.
Diseasefreesurvivalwasimprovedwithlongertamoxifenuse(69%versus57%,p<.0001witha
relativeriskof0.66,95%CI0.58-0.74),whiledistantdiseasefreesurvivalwasalsoimproved
withlongertamoxifenuse(76%versus67%,p<.0001withrelativerisk=0.70,95%CI 0.61-
0.81).
Domain7: CareFollowingInitialSurget7/Radiotherapy
Lackofcontinuityofcareisexperiencedbymanybreastcancerpatientsfollowinginitial
treatment. Researchfindingssuggestthatlackofcontinuity,inturn,resultsinreducedqualityof
life. Anumberofpapersreflectexpertopinionthatcoordinationandcommunicationamong
teammembershelpstoassurecontinuityofcare.^*^
Domain8: TreatmentofMorbidandComorbidSymptoms,Signs,andConditions
Withinthisdomainwefocusonthesymptoms,signs,andconditionsthatareprevalentamongst
womenwithbreastcancersincetheserepresentspatientconcernsthatrequiretreatment. We
focusonthesubsetofconditionsnotedtobeassociatedwithimprovedoutcomesifwomenare
treatedwithbetterascomparedwithworseprocesses. Thesemeasuresaredenvedfromthe
oncology,geriatnc,andqualityofcareliterature.
Theconditionofarmmorbidityfollowingaxillarynodedissectionand/orradiationforbreast
cancerrepresentgoodexamplesofprevalentconditionswhichcanbenefitfromtreatment. The
armsymptomsmaybecharacterizedasthedevelopmentoflymphedemaorotherarm
morbiditiessuchaspain,paresthesias,weaknessandimpairedshoulderfunction. Inastudyof
223patientsaftersurgeryfornon-recurrentbreastcancer,Maunselletal.foundincidencesof
armmorbidityat3monthsasfollows: swelling-24%,pain-55%,numbness-58%,weakness-
26%,limitationinrangeofmotion-32%,andstiffness-40%.^'™''^°°'""'"'"°"'*''"*'' At18month
follow-up,onlyrangeofmotionandlossofsensationhadimprovedby10%ormore. The
reportedincidenceoflymphedemafollowingbreastcancertherapyvarieswidely,Kissinreports
alymphedemarateof25%overallandarateof38%forthosepatientsreceivingaxillarynode
dissectionandradiationtherapy.^"'°''^°°'''""''"°"'*''"*''