Do variations in treatment of ductal carcinoma in situ affect outcomes?

128 Pages·2002·4.6 MB·English

by  Gold, Heather Taffet

0I-.043-TM
DoVariationsinTreatmentofDuctalCarcinomainSituAffectOutcomes?
by
HeatherTaffetGold
SubmittedinPartialFulfillment
ofthe
RequirementsfortheDegree
DoctorofPhilosophy
Supervisedby
ProfessorJackZwanziger
DepartmentofCommunityandPreventiveMedicine
TheSchoolofMedicineandDentistry
UniversityofRochester
Rochester,NewYork
2002
11
CurriculumVitae
HeatherTaffetGoldwasborninLosAngeles,CaliforniaonMay27,1970.
SheattendedtheUniversityofCaliforniaatSanDiegofrom1988to1992and
graduatedwithaBachelorofSciencedegreeinBiologyin1992.Shethenattended
theUniversityofChicagofrom1992to1994andgraduatedwithaMasterofArts
degreeinpublicpolicystudiesin1994.Ms.GoldcametotheUniversityof
Rochesterinthefallof1998andbegangraduatestudiesinhealthservicesresearch
andpolicy.ShereceivedaNationalResearchServiceAwardTraineeFellowshipin
1998and1999andaHealthCareFinancingAdministrationDissertationFellowship
in2001.Shepursuedherresearchinhealthservicesresearchandpolicyunderthe
directionofProfessorJackZwanzigerandwiththeguidanceofhercommittee
members,ProfessorsAndrewDick,CharlesPhelps,andJenniferGriggs.
Ill
Acknowledgements
Thisthesiswouldhavebeenmuchhardertofinishifitweren'tforsome
incrediblepeople.Firstly,mydissertationadvisor,JackZwanziger,PhD,hasbeena
greatmentorandprovidedmuchguidanceforthiswork.Hekeptmeontrackand
well-focused.Mycommitteemembershavealsobeenterrific,andIamgratefulfor
theirguidance.AndrewDick,PhD,spenthoursteachingmetheeconometric
modelingandStataprogrammingrequiredfortheanalysesandhelpedmehavea
senseofhumoraboutthedissertationprocess.JenniferGriggs,MD,MPH,offered
herclinicalexpertiseandprovidedmewith"real-life"experiencessoIcouldsee
whatpatientsactuallyfacedbecauseoftheirdisease.Andfinally,CharlesPhelps,
PhD,hasseenthe"bigpicture"allalongandprovidedtimelyfeedbackandgreat
adviceduringthischallengingendeavor.Iamindebtedtomycommitteeforallthe
timetheygaveme.
IamsoappreciativeofthedissertationfellowshipgrantIreceivedfromthe
HealthCareFinancingAdministration(HCFA),nowtheCenterforMedicareand
MedicaidServices(CMS),oftheUSDepartmentofHealthandHumanServices.
IacknowledgetheeffortsrequiredtolinktheSEERdatabasewiththe
Medicareclaimsdata,includingtheworkoftheAppliedResearchBranch,Division
ofCancerPreventionandControl,NationalCancerInstitute;theOfficeofResearch
andDemonstrationsatHCFA;andInformationManagementServices,Inc..
Finally,Iamgratefulforthesupportofmydearhusband,JeffreyTaffet,who
helpedmekeepabalanceinlifeespeciallythroughroughspots.
IV
Abstract
Ductalcarcinomainsitu(DCIS)isanoninvasiveformofbreastcancerwitha
distinctdiseasepathologyandnaturalhistorycomparedtoinvasivebreastcancer.Its
incidencehasincreasedsincethewidespreaduseofscreeningmammography.
Earlierdetectionofthediseaseandchangingtreatmentpatternsforearlyinvasive
breastcancerhaveledtotreatmentchangesforDCISwithoutanunderstandingof
thenaturalhistoryofDCIS.ThelackofinformationonthenaturalhistoryofDCIS
hasledtodoubtsaboutthebestwaytotreatitandhasgivenrisetosubstantial
variationsintreatmentpatternsforthedisease.
Theoverallobjectiveofthisprojectistoexaminetheeffectsofgeographic
andtemporalvariationinthetreatmentofwomendiagnosedwithunilateralDCIS.
Thestudywilltesttwomajorhypotheses:(1)thereisstatisticallysignificant
geographicandtemporalvariationinthetreatmentofwomenwithDCIS,bothin
typeofsurgery(mastectomyorbreast-conservingsurgery)anduseofradiotherapy;
and(2)variationintreatmentofDCIShasconsequencesforratesofrecurrenceof
DCISanddevelopmentofsubsequentinvasivebreastcancer.
ThisresearchisbasedondatafromtheSurveillance,EpidemiologyandEnd
Results(SEER)programlinkedwithMedicareclaimsdatafrom1991-1998,the
DartmouthAtlasofHealthCareintheUnitedStates,andUSCensusdata.The
longitudinal,observationalstudyuseseconometricmethodstoadvancethefieldof
measuringgeographicvariationandtoanalyzetheimpactoftreatmentchoice,region
effects,andsocioeconomicfactorsonpatientoutcomesforwomenages65and
older.
Geographiclocationandyearofdiagnosisaresignificantpredictorsof
treatmentchoiceforDCIS,indicatinggeographicandtemporalvariationintreatment
patterns.Theresultsoftheoutcomesanalysisstronglysuggestthattreatmentof
DCISwithmastectomyorbreast-conservingsurgery(BCS)withradiotherapyare
muchbetterthanwithBCSalone.Disease-freesurvival6yearsafterdiagnosisand
treatmentbymastectomyorBCSwithradiotherapyis96%comparedto86%for
BCSalone.TreatmentwithmastectomyorBCSwithradiotherapyproducessuperior
outcomescomparedtoBCSalonewhichistheworstintermsofdisease-free
survival.
VI
TableofContents
page
ListofTables vii
ListofFigures ix
Chapter1 Background 1
Introduction 1
BackgroundandSignificance 2
Summary 18
Chapter2 DataandMethods 19
Data 19
Methods 32
Software 48
Chapter3 Results 49
GeographicVariationsResults 49
OutcomesAnalysisComparingBCS,BCSwith 62
Radiotherapy,andMastectomy
Chapter4 Discussion 78
TreatmentOutcomes 78
VariationsinTreatmentChoice 82
DataLimitations 86
ModelLimitations 90
AreasforFutureWork 91
Conclusion 92
References 94
AppendixA ComorbidityIndices 107
AppendixB OutcomesAnalysisofMastectomyOnly 110
.
Vll
ListofTables
page
Table2-1. DataandExclusionsforInitialSampleofCasesandfor 21
AnalyticSamplesofLinkedSEER-MedicareData,1986-
1998.
Table2-2. MedicareClaimsandSEERCodesUsedtoDetermine 25
InitialTreatment.
Table2-3. MedicareClaimsCodesUsedtoDetermineSubsequent 28
BreastEvents.
Table2-4. HypothesizedEffectsofVariablesonProbabilityof 38
ChoosingBCS,BCSwithRadiotherapy,orMastectomy,
1991-1996.
Table2-5. HypothesizedEffectsofVariablesonDCISTreatment 47
Outcomes,1991-1998.
Table3-1 InitialTreatmentTypeandComparisonofMeansof 55
DemographicFactorsforGeographicVariationsAnalysis
BasedonLinkedSEER-MedicareDatabase,1991-1996.
Table3-2. MultinomialLogitModelCoefficientEstimatesfor 57
ProbabilityofTreatmentChoiceComparedtoBreast-
conservingSurgeryAlone,1991-1996.
Table3-3. PredictedPercentageUseofInitialTreatmentforDuctal 59
Carcinomainsitu,basedonLinkedSEER-Medicare
Database,1991-1996.
Table3-4. ObservedSampleStandardErrorsandConfidenceIntervals 60
forProbabilityofChoosingTreatmentOptionObtainedby
Bootstrapping400Times.
Table3-5. InitialTreatmentTypeandSubsequentBreastEventsfor 64
WomenDiagnosedwithDCISinFinalOutcomes-Analysis
SamplefromLinkedSEER-MedicareDatabase,1991-1996.
Table3-6. InitialTreatmentTypeandComparisonofDemographic 65
FactorsforOutcomesAnalysisbasedonLinkedSEER-
MedicareDatabase,1991-1996.
Vlll
Table3-7. CoefficientEstimatesfromSemiparametricOutcomes 69
ModelwithIndicatorsforEachTimePeriod.
Table3-8. CoefficientEstimatesfromSemiparametricOutcomes 71
ModelwithParametricDuration.
Table3-9. PredictedProportionofSubsequentBreastEventsandof 72
Disease-freeSurvivalfromPeriod-to-Period,Conditionalon
HavingNoSubsequentBreastEventinPriorPeriodand
BasedonMeanValuesofCovariates.
Table3-10. DifferencesinSurvivalCurves,BasedonOutcomesModel 77
withParametricDurationandaStandardizedPopulation,
Bootstrapped100Times.
TableA-l. ConditionCoefficientsforComorbiditiesDerivedfrom 109
MedicareClaimsDatafortheBreastCohort.
TableB-l. DescriptiveStatisticsofDemographicFactorsforOutcomes Ill
AnalysisforMastectomyOnlybasedonLinkedSEER-
MedicareDatabase,1986-1996.
TableB-2. CoefficientsforSemiparametricMastectomy-OnlyModel 113
withIndicatorsforEachTimePeriod,1986-1998.
TableB-3. CoefficientsforSemiparametricMastectomy-OnlyModel 114
withParametricDuration,1986-1998.
TableB-4. HazardRatesandDisease-freeSurvivalafterMastectomy 116
Only,SemiparametricModels,1986-1998.
..
IX
ListofFigures
page
Figure3-1 StandardDeviationofTreatmentProbabilityAcross 61
Registries,byTreatmentStrategyandYear.
Figure3-2. ProbabilityofSubsequentBreastEvent, 73
SemiparametricModelwithDurationIndicator
Variables.
Figure3-3. Disease-freeSurvival,SemiparametricModelwith 74
DurationIndicatorVariables.
Figure3-4. ProbabilityofSubsequentBreastEvent, 75
SemiparametricModelwithSingleDurationVariable.
Figure3-5. Disease-freeSurvival,SemiparametricModelwith 76
SingleDurationVariable.
FigureB-1 ProbabilityofSubsequentBreastEventafter 117
MastectomyforDCIS,1986-1998.
FigureB-2. Disease-freeSurvivalafterMastectomyforDCIS, 118
1986-1998.
Chapter1
Background
Introduction
Ductalcarcinomainsitu(DCIS)isanoninvasiveformofbreastcancerwitha
distinctdiseasepathologyandnaturalhistorycomparedtoinvasivebreastcancer.
DCIStypicallypresentsasasymptomaticcalcificationsoflessthan10mmon
mammography,andthepresumablymalignantcellsremainatthesiteoforigininthe
ducts(1,2).Unlikeinvasivebreastcancer,DCISisnotassociatedwiththeriskof
metastaticdisease.DCIS,bydefinition,doesnotinvadethebasementmembraneor
metastasize.Thediseasecandevelopintoalocalinvasiverecurrenceinthebreast,
however,thatcouldleadtobreastcancermetastasisandmortality(3).
Approximately50%oflocalrecurrencesfollowingDCISdiagnosisandtreatmentare
invasive(1),butthe10-yearriskofbreastcancerdeathislowatunder2%(4).
ThetreatmentoptionsforDCISaresimilartothoseforearlybreastcancer:
mastectomyorbreast-conservingsurgery(BCS)withorwithoutradiotherapyand
morerecently,withorwithouttheadditionofhormonaltherapysuchastamoxifen.
ThecontroversiesovertreatmentforDCISexistbecauseitisunclearwhichwomen
mightdobetterafteratotalmastectomyormightbenefitfromradiotherapyin
additiontoBCS.DCISisinterestingtostudybecauseofthedownstreammortality
risksassociatedwithasubsequentbreastevent-thatis,arecurrenceofDCISor
developmentofinvasivebreastcancer-andtheincreasingincidenceofthedisease
(1),aswellasthequality-of-lifetrade-offsassociatedwiththedifferenttreatment