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Metastatic breast cancer survival improvement restricted by regional disparity: Surveillance, Epidemiology, and End Results and institutional analysis: 1990 to 2011 390 Cancer January 15, 2020 Original Article Metastatic Breast Cancer Survival Improvement Restricted by Regional Disparity: Surveillance, Epidemiology, and End Results and Institutional Analysis: 1990 to 2011 Judith A. Malmgren, PhD 1,2; Gregory S. Calip, PharmD, MPH, PhD 3; Mary K. Atwood, CTR4; Musa Mayer, MS, MFA5; and Henry G. Kaplan, MD4 BACKGROUND: The extent of breast cancer outcome disparity can be measured by comparing Surveillance, Epidemiology, and End Results (SEER) breast cancer-specific survival (BCSS) by region and with institutional cohort (IC) rates. METHODS: Patients who were diagnosed with a first primary, de novo, stage IV breast cancer at ages 25 to 84 years from 1990 to 2011 were studied. The change in 5-year BCSS over time from 1990 to 2011 was compared using the SEER 9 registries (SEER 9) without the Seattle-Puget Sound (S-PS) region (n = 12,121), the S-PS region alone (n = 1931), and the S-PS region IC (n = 261). The IC BCSS endpoint was breast cancer death con- firmed from chart and/or death certificate and cause-specific survival for SEER registries. BCSS was estimated using the Kaplan-Meier method. Hazard ratios (HzR) were calculated using Cox proportional-hazards models. RESULTS: For SEER 9 without the S-PS region, 5-year BCSS improved 7% (from 19% to 26%) over time, it improved 14% for the S-PS region (21% to 35%), and it improved 27% for the S-PS IC (29% to 56%). In the IC Cox proportional-hazards model, recent diagnosis year, chemotherapy, surgery, and age <70 years were="" associated="" with="" better="" survival.="" for="" seer="" 9,="" additional="" significant="" factors="" were="" white="" race="" and="" positive="" hormone="" receptor="" status="" and="" s-ps="" region="" was="" associated="" with="" better="" survival="" (hzr,="" 0.87;="" 95%="" ci,="" 0.84-0.90).="" in="" an="" adjusted="" model,="" hazard="" of="" bc="" death="" decreased="" in="" the="" most="" recent="" time="" period="" (2005-2011)="" by="" 28%="" in="" seer="" 9="" without="" s-ps,="" 43%="" in="" the="" s-ps="" region="" and="" 45%="" in="" the="" ic="" (hzr,="" 0.72="" [95%="" ci,="" 0.67-0.76],="" 0.57="" [95%="" ci,="" 0.49-0.66],="" and="" 0.55="" [95%="" ci,="" 0.39-0.78],="" respectively).="" conclusions:="" over="" 2="" decades,="" the="" survival="" of="" patients="" with="" metastatic="" breast="" cancer="" improved="" nationally,="" but="" with="" regional="" survival="" disparity="" and="" differential="" improvement.="" to="" achieve="" equitable="" outcomes,="" access="" and="" treatment="" approaches="" will="" need="" to="" be="" identified="" and="" adopted.="" cancer="" 2020;126:390-399.="" ©="" 2019="" the="" authors.="" cancer="" published="" by="" wiley="" periodicals,="" inc.="" on="" behalf="" of="" american="" cancer="" society.="" this="" is="" an="" open="" access="" article="" under="" the="" terms="" of="" the="" creative="" commons="" attribution-noncommercial-noderivs="" license,="" which="" permits="" use="" and="" distribution="" in="" any="" medium,="" provided="" the="" original="" work="" is="" properly="" cited,="" the="" use="" is="" non-commercial="" and="" no="" modifications="" or="" adaptations="" are="" made.="" keywords:="" differential="" survival,="" disease-specific="" survival="" (dss),="" metastatic="" breast="" cancer,="" regional="" disparity.="" introduction="" variation="" in="" breast="" cancer="" recurrence="" and="" survival="" may="" be="" influenced="" by="" age,="" race,="" access="" to="" care,="" insurance="" coverage,="" socioeconomic="" status,="" geographic="" area="" of="" residence="" (urban/rural="" or="" metropolitan/nonmetropolitan),="" and="" timely="" diagnosis="" and="" treatment.1-4="" from="" national="" statistics,="" factors="" contributing="" to="" state="" variations="" in="" cancer="" incidence="" rates="" include="" risk="" factor="" prevalence,="" access="" to="" and="" utilization="" of="" early="" detection="" services,="" and="" completeness="" of="" reporting.5="" despite="" survival="" improvements="" across="" poverty="" levels="" for="" all="" stages="" of="" disease,="" relative="" survival="" remains="" lower="" among="" women="" residing="" in="" poor="" areas="" compared="" with="" affluent="" women.6="" some="" evidence="" links="" guideline="" compliance="" to="" improved="" and="" optimal="" outcomes,="" but="" a="" lack="" of="" ability="" to="" compare="" guideline="" adherence="" in="" national="" databases="" inhibits="" the="" ability="" to="" evaluate="" widespread="" adherence="" or="" efficacy.7,8="" we="" previously="" observed="" significant="" improvement="" in="" 5-year="" disease-specific="" survival="" of="" patients="" with="" de="" novo="" stage="" iv="" metastatic="" breast="" cancer="" (mbc)="" over="" time="" from="" 1990="" to="" 2010="" without="" a="" concurrent="" improvement="" in="" the="" survival="" of="" pa-="" tients="" with="" recurrent="" mbc="" from="" our="" study="" of="" an="" institutional="" cohort="" of="" breast="" cancer="" registry="" patients.9="" the="" 5-year="" breast="" cancer-specific="" survival="" (bcss)="" rates="" in="" our="" institutional="" cohort="" of="" patients="" with="" stage="" iv="" breast="" cancer="" were="" significantly="" higher="" than="" the="" rates="" previously="" reported="" for="" stage="" iv="" breast="" cancer="" from="" surveillance,="" epidemiology,="" and="" end="" results="" (seer)="" registry="" data.10="" regional="" disparity="" in="" breast="" cancer="" outcomes="" can="" be="" measured="" by="" comparing="" bcss="" rates="" from="" seer="" across="" geo-="" graphic="" regions="" and="" with="" the="" rates="" from="" a="" seer-embedded="" institutional="" cohort.="" we="" compared="" seer="" aggregate="" data="" to="" corresponding="" author:="" judith="" a.="" malmgren,="" phd,="" 12025="" ninth="" avenue="" nw,="" seattle,="" wa="" 98177;=""
[email protected]="" 1="" healthstat="" consulting,="" inc.,="" seattle,="" washington;="" 2="" department="" of="" epidemiology, university="" of="" washington,="" seattle,="" washington;="" 3="" center="" for="" pharmacoepidemiology="" and="" pharmacoeconomic="" research, university="" of="" illinois="" at="" chicago,="" chicago,="" illinois;="" 4="" swedish="" cancer="" institute,="" seattle,="" washington;="" 5="" metastatic="" breast="" cancer="" alliance,="" new="" york,="" new="" york="" we="" acknowledge="" and="" sincerely="" thank="" dr.="" marc="" hurlbert="" for="" his="" invaluable="" assistance.="" doi:="" 10.1002/cncr.32531,="" received:="" may="" 10,="" 2019;="" revised:="" august="" 25,="" 2019;="" accepted:="" august="" 30,="" 2019,="" published="" online="" october="" 22,="" 2019="" in="" wiley="" online="" library="" (wileyonlinelibrary.com)="" mailto:="" https://orcid.org/0000-0001-6939-8828="" https://orcid.org/0000-0002-7744-3518="" http://creativecommons.org/licenses/by-nc-nd/4.0/="" mailto:
[email protected]="" metastatic="" breast="" cancer="" survival="" disparity/malmgren="" et="" al="" 391cancer="" january="" 15,="" 2020="" the="" regional="" subset="" from="" the="" seattle-puget="" sound="" (s-ps)="" area="" registry="" and="" to="" an="" institutional="" cohort="" (ic)="" located="" in="" the="" s-ps="" registry="" area="" whose="" cases="" are="" included="" in="" the="" s-ps="" cancer="" surveillance="" system="" (seer="" 9="" without="" s-ps,="" n="12,121;" s-ps,="" n="1931;" and="" seattle="" ic,="" n="261)." our="" objectives="" were="" to="" compare="" survival="" rates="" to="" evaluate="" regional="" disparity="" in="" de="" novo="" mbc="" survival,="" to="" compare="" survival="" rate="" improvement="" over="" time="" by="" region="" and="" insti-="" tution,="" and="" to="" assess="" the="" impact="" of="" temporal="" advances="" in="" systemic="" therapies="" on="" trends="" in="" de="" novo="" stage="" iv="" mbc="" survival="" rates.="" in="" particular,="" our="" focus="" was="" on="" regional="" survival="" differences="" and="" the="" potential="" for="" survival="" rate="" improvement="" over="" time="" as="" patients="" with="" metastatic="" disease="" have="" a="" poor="" prognosis="" and="" are="" often="" treated="" with="" palliative="" rather="" than="" with="" stabilizing="" or="" curative="" intent.="" materials="" and="" methods="" the="" analysis="" included="" patients="" aged="" 25="" to="" 84="" years="" with="" first="" primary="" breast="" cancer="" who="" were="" diagnosed="" with="" de="" novo="" stage="" iv="" breast="" cancer="" from="" 1990="" to="" 2011="" in="" the="" seer="" 9="" registries="" and="" an="" institutional="" cohort="" (ic)="" located="" in="" the="" seer="" 9="" s-ps="" region="" (vital="" status="" through="" 2016).="" we="" calculated="" 5="" -year="" breast="" cancer-specific="" sur-="" vival="" (bcss)="" for="" 3="" time="" periods="" (1990-1998,="" 1999-2004,="" and="" 2005-2011),="" during="" which="" adjuvant="" chemotherapy="" treatments="" changed="" significantly="" and="" was="" available="" for="" the="" ic="" patients="" (table="" 1).11="" for="" the="" ic,="" the="" bcss="" end-="" point="" was="" breast="" cancer="" death="" confirmed="" from="" chart="" and/="" or="" death="" certificate.="" for="" seer,="" seer*stat-documented="" cause-specific="" survival="" was="" used.12="" the="" seer="" s-ps="" region="" was="" used="" separately="" for="" comparison="" with="" seer="" 9="" without="" s-ps="" and="" the="" ic.="" five-year="" bcss="" and="" 95%="" cis="" and="" cox="" proportional="" hazard="" models="" were="" calculated="" using="" spss="" 25.0="" (ibm="" corporation)="" for="" the="" institutional="" cohort="" and="" stata="" (statacorp="" llc)="" for="" seer="" 9.13,14="" bcss="" was="" estimated="" as="" the="" net="" measure="" representing="" survival="" from="" death="" caused="" by="" the="" primary="" diagnosed="" breast="" cancer="" in="" the="" absence="" of="" other="" causes="" of="" death.="" patients="" who="" died="" of="" causes="" other="" than="" those="" specified="" were="" considered="" to="" be="" censored.15="" cox="" proportional="" hazards="" modelling="" was="" used="" to="" es-="" timate="" adjusted="" hazard="" ratios="" (hzr)="" with="" corresponding="" 95%="" cis,="" with="" death="" from="" disease="" as="" the="" endpoint.="" the="" ic="" was="" used="" to="" build="" an="" a="" priori="" model="" informed="" by="" a="" chi-square="" analysis="" and="" tested="" by="" stepwise="" entry="" into="" the="" model="" with="" a="" subsequent="" forced-entry="" model="" to="" include="" all="" variables="" of="" interest="" in="" the="" seer="" 9="" population.="" the="" proportional="" hazards="" assumption="" was="" evaluated="" graph-="" ically="" using="" the="" log(-log[survival])="" versus="" log="" of="" survival="" time.="" we="" found="" no="" evidence="" suggesting="" violation="" of="" the="" proportionality="" assumption.="" all="" p="" values="" were="" 2-sided="" using="" a="" .05="" level="" of="" significance.="" data="" from="" the="" seer="" 9="" population-based="" cancer="" registries="" (connecticut,="" detroit,="" atlanta,="" san="" francisco-="" oakland,="" hawaii,="" iowa,="" new="" mexico,="" seattle-puget="" sound,="" and="" utah)="" were="" included="" in="" our="" analysis.16="" the="" seer="" pro-="" gram="" is="" funded="" by="" the="" national="" institutes="" of="" health="" and="" the="" national="" cancer="" institute="" and="" represents="" cancer="" incidence="" data="" for="" approximately="" 28%="" of="" the="" us="" population.="" the="" institutional="" cohort="" (ic)="" breast="" cancer="" registry="" database,="" which="" was="" created="" in="" 1990,="" contains="" detailed="" information="" on="" diagnosis,="" pathology,="" staging,="" surgery,="" chemotherapy,="" radiation="" therapy,="" tumor="" markers,="" and="" vital="" status="" at="" follow-up,="" including="" cause-specific="" death.="" incident="" breast="" cancer="" cases="" are="" entered="" at="" the="" time="" of="" diag-="" nosis="" in="" a="" health="" insurance="" portability="" and="" accountability="" act="" of="" 1996="" (hipaa)-compliant="" and="" institutional="" review="" board="" (irb)-approved="" research="" registry.="" this="" project="" was="" hipaa="" compliant="" and="" irb="" approved.="" patient="" vital="" and="" disease="" status,="" including="" date,="" site="" and="" type="" of="" recurrence,="" and="" date="" and="" cause="" of="" death,="" is="" collected="" prospectively="" through="" annual="" updates="" by="" a="" certified="" cancer="" registrar.="" follow-up="" is="" obtained="" from:="" 1)="" electronic="" chart="" review;="" 2)="" an="" irb-approved,="" physician-directed="" follow-up="" letter;="" 3)="" an="" institutional="" cancer="" registry;="" and="" 4)="" the="" seer="" s-ps="" registry.17="" table="" 1.="" change="" in="" systemic="" therapy="" from="" 1990="" to="" 2011:="" stage="" iv="" breast="" cancer,="" ic="" patients="" only, n =" 261" systemic="" therapy="" no.="" of="" patients="" (%)="" p1990-1998="" 1999-2004="" 2005-2011="" initial="" chemotherapy,="" n =" 175" 51="" (64)="" 40="" (66)="" 84="" (70)="" .629="" taxane="" therapy,="" n =" 99" 11="" (21)="" 24="" (60)="" 64="" (76)=""><.001 anthracycline="" therapy,="" n =" 114" 43="" (83)="" 28="" (70)="" 43="" (51)="" .001="" trastuzumab="" therapy:="" her-2–positive="" patients,="" n =" 45" 0="" (0)="" 8="" (68)="" 25="" (100)=""><.001 neoadjuvant therapy, n = 64 18 (23) 7 (12) 39 (33) .007 hormone therapy: hr-positive patients, n = 193 48 (86) 41 (89) 83 (91) .583 abbreviation: hr, hormone receptor. original article 392 cancer january 15, 2020 results the seer 9 without s-ps population and the seer s-ps region population were both older than the ic patients (mean age, 61 vs 55 years). more ic and s-ps patients identified as white race (ic, 81%; s-ps, 89%) than seer 9 without s-ps patients (75%) (table 2). of all invasive breast cancers in the populations, 5% of those in seer 9 without s-ps, 4% of those in the s-ps region, and 3% of those in the ic were de novo stage iv. patients in the s-ps region and in the ic were more often hormone recep- tor (hr)-positive (66% and 74%, respectively, vs 56% in seer 9 without s-ps). stage iv surgical treatment was received by ≥50% of patients in all 3 groups (seer 9 without s-ps, 58%; s-ps, 56%; ic, 50%). patients in the neoadjuvant="" therapy,="" n =" 64" 18="" (23)="" 7="" (12)="" 39="" (33)="" .007="" hormone="" therapy:="" hr-positive="" patients,="" n =" 193" 48="" (86)="" 41="" (89)="" 83="" (91)="" .583="" abbreviation:="" hr,="" hormone="" receptor.="" original="" article="" 392="" cancer="" january="" 15,="" 2020="" results="" the="" seer="" 9="" without="" s-ps="" population="" and="" the="" seer="" s-ps="" region="" population="" were="" both="" older="" than="" the="" ic="" patients="" (mean="" age,="" 61="" vs="" 55="" years).="" more="" ic="" and="" s-ps="" patients="" identified="" as="" white="" race="" (ic,="" 81%;="" s-ps,="" 89%)="" than="" seer="" 9="" without="" s-ps="" patients="" (75%)="" (table="" 2).="" of="" all="" invasive="" breast="" cancers="" in="" the="" populations,="" 5%="" of="" those="" in="" seer="" 9="" without="" s-ps,="" 4%="" of="" those="" in="" the="" s-ps="" region,="" and="" 3%="" of="" those="" in="" the="" ic="" were="" de="" novo="" stage="" iv.="" patients="" in="" the="" s-ps="" region="" and="" in="" the="" ic="" were="" more="" often="" hormone="" recep-="" tor="" (hr)-positive="" (66%="" and="" 74%,="" respectively,="" vs="" 56%="" in="" seer="" 9="" without="" s-ps).="" stage="" iv="" surgical="" treatment="" was="" received="" by="" ≥50%="" of="" patients="" in="" all="" 3="" groups="" (seer="" 9="" without="" s-ps,="" 58%;="" s-ps,="" 56%;="" ic,="" 50%).="" 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