Acta MedPort2014May-Jun;27(3):xxx-xxx Recebido: 26de Agosto de2013- Aceite: 11 deNovembro2013| 2. SouthernPortugalCancerRegistry(ROR-Sul). InstitutoPortuguêsdeOncologiaLisboaFranciscoGentil.Lisbon.. 1. DepartmentofMedicalOncology. InstitutoPortuguêsdeOncologiaLisboaFranciscoGentil.Lisbon.Portugal. year per deaths 000 458 and cases million 1.4 in women in cancer developed common countries. Worldwide, the estimated incidence of most the and worldwide INTRODUCTION RESUMO Maria doROSÁRIO ANDRÉ ets respectively. deaths, cancer total of 14% and cases cancer new total of 23% to ABSTRACT Registo OncológicoRegionalSul Sobrevivência deCancrodaMamaeFactores Associados: Resultadosdo Cancer RegistryinPortugal Factors: ReportedOutcomesfromtheSouthern Breast CancerPatientsSurvivaland Associated Palavras-chave: entanto, nãoforamobservadasdiferençasnasobrevivênciaentre diferentesregiõesgeográficasderesidência. Conclusões: biológicas tumorais parecem ser os principais factores associados à sobrevivência do cancro de mama feminino na nossa população. características regiões. As estas entre mama de cancro do sobrevivência na discrepâncias de existência a suportam não resultados nossos os geográficas, regiões entre tumorais sub-tipos de e etária distribuição na observadas diferenças das Apesar Discussão: diferenças nasobrevivênciaentremulheresresidentesemregiõesgeográficasdistintas. aos 5 anos foi de 80%, com uma associação significativa com o estadio, receptores hormonais e status HER2. Não foram identificadas HER2- tumores de Região . na da HER2-negativo Autónoma Atumores estimada de global incidência incidência sobrevivência no maior positivo e maior uma com tumorais, sub-tipos de distribuição na Alentejo; no envelhecida população uma com Resultados: Foram incluídos neste estudo 1 354 doentes. Observaram-se as seguintes variações geográficas: na distribuição etária, dados doRegistoOncológicoRegionalSul(ROR-Sul)ecomplementadoscomdosprocessosclínicos. de base da partir a recolhidos sido dados os tendo Portugal, de sul região na residentes e 2005 em diagnosticados mama de cancro de casos incluídos Foram follow-up. com retrospectiva, orientação e populacional base de coorte, de Estudo Material eMétodos: mama femininoeosprincipaisfactoresassociados. biológicas tumorais, e o acesso aos cuidados de saúde. O objectivo deste estudo é detectar diferenças na sobrevivência do cancro de São múltiplos os factores que podem influenciar esta distribuição, incluindo aspectos demográficos e socioeconómicos, características na mulher. As taxas de mortalidade por cancro de mama apresentam uma distribuição heterogénea nas diferentes regiões de Portugal. Objectivos: A incidência do cancro da mama em Portugal é inferior à média europeia, sendo, ainda assim, a neoplasia mais frequente Keywords: BreastNeoplasms;NeoplasmStaging;Survival Analysis; Portugal. However, nodifferences inpatientsurvivalwereobserved amongdifferent regionsofresidence. Conclusions: the mainassociatedfactorwithbreastcancersurvivalinourpopulation. be to seem characteristics biological Tumorregions. these between survival cancer breast in discrepancies of existence the support not does study our regions, geographical between distribution sub-type tumor and age differencesin Discussion: found we Although from distinctgeographicalregions. women among identified were differences survival No status. HER2 and receptor hormone stage, tumor with association significant higher incidence of HER2-negative tumors in Região Autónoma da Madeira. Reported estimated 5-year overall survival was 80%, with a and the Algarve in tumors HER2-positive of incidence higher a was there sub-types, tumor for in Alentejo; population aging an with distribution, age for follows: as were variations geographical study.Observed this in included were patients 354 1 of Results: Atotal Cancer Registry(ROR-Sul)databaseandcompletedwithclinicalchartinformation. cancer breast Incident cases diagnosed in 2005 follow-up. of residents in the southern region of Portugal were included. with Data was collected from the Southern Portugal study cohort retrospective population-based, a conducted have We Material andMethods: female breastcancerandidentifythemainassociatedfactors. in differences survival detect to is study this of aim The care. medical to access and characteristics, biological tumor aspects, nomic socioeco and demographic include may factors Implicated Portugal. throughout heterogeneous are rates mortality in Overall, cancer women. frequent most the is it average, European the than lower is Portugal in incidence cancer breast the Although Objectives: rat acr s h scn ms cmo cancer common most second the is cancer Breast Our study confirms the association between patient survival and tumor stage, hormone receptor and HER2 status. HER2 and receptor hormone stage, tumor and survival patient between association the confirms study Our O nosso estudo confirma a associação entre a sobrevivência e o estadio, receptores hormonais e status HER2. No HER2. status e hormonais receptores estadio, o e sobrevivência a entre associação a confirma estudo nosso O NeoplasiasdaMama;EstadiamentodeNeoplasias; Análise deSobrevida;Portugal. 2 n eet er, h bes cancer breast the years, recent In ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R 1 , Sandra AMARAL Copyright ©Ordemdos Médicos2014 1 correspond 1 , Alexandra MAYER 1 niec rts ae en nraig hogot the throughout increasing been world. have rates incidence n ot onre, oal ms afcig oe ae > years. 50 aged women affecting most notably countries, most in 1990s the to 1970s the from 30-40% of increase an show an annual decline of 2.3% in age-adjusted breast cancer- breast age-adjusted in 2.3% of decline annual an 2 3 , Ana MIRANDA g-dutd niec rts vr he decades three over rates incidence Age-adjusted 4 In contrast, mortality rates have decreased with decreased have rates mortality contrast, In 2 , ROR-SUL Working Group 2

DICA PORT É UG M U TA E C S - A A

1979 - 2014 35

s anos

a

c

i

3

d 5

é

a

m n

o o

i

s

b

a

s

a p

i

r

c

o

n

m

ê

i

o c

v s e r a

ARTIGO ORIGINAL Data 20 Staging of Staging 19 Edition. th revision. rd Acta Med Port 2014 May-Jun;27(3):xxx-xxx May-Jun;27(3):xxx-xxx Port 2014 Acta Med Frequencies were calculated for variables related to A total of 2 821 breast cancer cases diagnosed Patients included in this study had confirmed female and classification histological site), (primary Topography breast cancer was classified according to the American Joint American the to according classified was cancer breast Committee on Cancer Criteria (AJCC), 6 was extracted from ROR-Sul database and supplemented needed. as charts clinical the from information medical with Collected variables included demographic characteristics (birth date, age at diagnosis, place of residence), clinical characterization (date of first medical consultation, date of diagnosis, topography, histology, tumor histological grade, receptor factor growth epidermal human status, PR and ER 2 (HER2) expression, stage), treatment disease options therapy), hormone (surgery, and radiotherapy chemotherapy, status (if death, date of death; if relapse, date of relapse). date was December 31, 2010. Cut-off Data analysis demographic, clinical and pathologic determine their characteristics overall to distribution, among among stages geographical and were calculated regions. by the mean Quantitative data or distribution. median The variables depending differences on in between variable geographical regions distribution were examined using Chi- (quantitative square (qualitative variables) test ANOVA and variables) to obtain p-values. USA. Data Windows, for 12.0 Stata/SE and 2007 Excel Microsoft was analyzed using Statistical significance was assessed by two-tailedwith an alpha tests level of 0.05. Survival was calculated by the Kaplan-Meyer method and compared using Log-Rank test. RESULTS throughout 2005 were registered in Of ROR-Sul these, database. 2 725 cases Southern Portugal were territory at the time effectively of diagnosis (2 150 resident in the from Lisboa e Vale do (LVT), Tejo 277 from Alentejo, 193 from Algarve and 105 from Região Autónoma da Madeira LVT the in were cases of majority vast the Because (RAM)). region (79%), only 55% of these were randomly selected to be included in the study. After randomization we the had population the of have 45% remaining the that confirmed This study was approved Committee of the Portuguese by Institute of Oncology-Lisbon. the scientific andConfidentiality ethical was procedures established maintained by Portuguese Law. According to under is record database the containing file the legislation, current correspondent registered in the National Commission for Data Protection, (No. 1973500003). as of December 1997 Selection of patients primary breast cancer diagnosed between January 1, 2005 and December 31, 2005, and were residents in the south the time of diagnosis. region of Portugal at Criteria Pathologic Diagnostic 3 ICD-O, the on based were behavior 2

1 17 and 6 In , 5 with an age- 15 . Overall, mortality 16 It includes the regions 18 However, improvements In addition to demographic to addition In 7 12 In Portugal, breast cancer 14 and encompasses a population R e v i s ta C i e n tífi c a d a Or d e m d o s M é d i c o s w w w.a c ta m e d i c a p o r tu g u e s a .c o m 2 Furthermore, women with estrogen receptor Rosário André M, et al. Geographical variations in breast cancer epidemiology, epidemiology, breast cancer variations in Geographical M, et al. André Rosário 13 In addition, women with lower socioeconomic 8-11 We We have conducted a population-based retrospective (ER)-positive and/or progesterone receptor (PR)-positive tumors have a better prognosis than those with hormone receptor-negative tumors. rates seem to differ regions, between with Portuguese a mortality geographical rate of 000 in 14.4/1 Alentejo, 000 11.6/1 9.5/1 in do Tejo, Lisboa e Vale 000 inhabitants in Algarve and 000 11.0/1 in Autónoma Região da Madeira. in survival have not been homogeneous, as suggested by epidemiologic studies among women with breast cancer. Race/ethnic disparities persist in survival. cancer incidence and of Lisboa e Vale do Tejo (Lisboa, Santarém and Setúbal districts), Alentejo (Portalegre, Évora and Beja districts), Algarve (Faro district) and Região Autónoma da Madeira. Autónoma Região da Madeira is a Portuguese archipelago with political and administrative the North autonomy, Atlantic Ocean, and localized composed of two inhabited in islands (Madeira and Porto Santo Islands) and two groups of uninhabited islands (Desertas and Savage Islands). status have a higher risk of being diagnosed with advanced with diagnosed being of risk higher a have status disease, and rates. of survival lower consequent receiving inadequate treatment, with study of female breast cancer cases Portugal from the Southern Cancer which 1988, in established registry Registry cancer population-based (ROR-Sul). ROR-Sul includes the south is region of Portugal. This a region covers a territory of 39 500 km MATERIAL AND METHODS MATERIAL Study Design Hence, the scope of the present work relies on acquiring a cancer breast for patterns survival of understanding deeper patients in the Portuguese report the population. breast cancer profile Specifically, - survival we differences and associated factors - among women living in the southern region of Portugal. The major goal provide of updated the information authors to is to support towards national the reduction actions or elimination of disparities among Portuguese women with breast cancer. Breast cancer mortality rates have estimated an with decade last the also in population Portuguese declined in the annual percent change of -2% per year, with declines the observed in largest the regions that had higher mortality rates at the beginning of the period related related mortality from 1990-2002 in the USA. similar trends were observed in 2000, and 1980 between 15% of reductions with rates, breast cancer mortality of almost 4.5 million inhabitants. and socioeconomic factors, it is well established that tumor biological characteristics influence prognosis and survival. Patients with histological Grade overall 3 survival when compared with patients with Grade 1 tumors have poorer or 2 tumors. standardized incidence rate of 60.0/100 000 females. 6.9% between 2002 and 2007. ranks first among cancers affecting women,

ARTIGO ORIGINAL Table 1 1354 included cases. analysis final Hence, disease). invasive breast corroborate not did reports histopathological 2005 from different was diagnosis of date (e.g. criteria inclusion on inconsistencies to due analysis final the from excluded health Portuguese institutions). Following different appropriate revision, 399 cases from were charts clinical 104 2 to (corresponding 753 1 was study present the for reviewed cases of number Total included. were regions other from cases 575 All ones. included the as characteristics same IV III II I Stage, n(%) HR-/HER2- HR-/HER2+ HR+/HER2- HR+/HER2+ Tumor biologicvariants, Positive Negative PR, n(%) Positive Negative ER, n(%) >65 40-65 <40 Age Distribution, No. ofpatients(%) Characteristic Positive Negative HER2, n(%) Others InflammatoryCarcinoma MucinousCarcinoma LobularandDuctalCarcinoma InvasiveLobularCarcinoma InvasiveDuctalCarcinoma Morphology, n(%) -ClinicalandDemographicCharacteristics Rosário André M,etal.Geographicalvariationsinbreastcancerepidemiology, n (%) n (%) ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R LVT 770 (85,1) 141 (17) 327 (40) 292 (36) 384 (49) 230 (29) 615 (79) 165 (21) 905 (67) 355 (45) 381 (42) 456 (50) 150 (19) 534 (68) 73 (8,1) 13 (1,4) 10 (1,1) 38 (4,2) 90 (11) 1 (0,1) 53 (7) 64 (8) 44 (6) 68 (8) 3 f ains le ta 6-er od. h ms frequent most The old). 65-years than older 50% patients (> Alentejo of in population aging an with distribution age in variations geographical observed We age. of years 65 and 40 between diagnosed were patients of 50% and years) 97 of maximum a and 22 of minimum a years, 14 of deviation standard a (with years 61 was diagnosis mean at The age RAM. from patients 97 and Algarve from 166 LVT,Alentejo, from from patients patients 186 905 follows: as distributed were cases Evaluated Table1. in presented are characteristics Patient institutions. health Portuguese Patient’s characteristics ttl f 34 ains ee nldd rm 27 from included were patients 354 1 of total A Alentejo 186 (14) 102 (66) 142 (76) 103 (55) 117 (75) 28 (17) 60 (36) 65 (40) 88 (57) 18 (12) 31 (20) 93 (60) 51 (33) 36 (23) 27 (15) 67 (36) 16 (9) 11 (7) 11 (7) 9 (6) 3 (2) 4 (2) 4 (2) 6 (3) Acta MedPort2014May-Jun;27(3):xxx-xxx Algarve 166 (12) 129 (78) 113 (73) 31 (20) 56 (35) 58 (37) 18 (12) 67 (43) 33 (21) 38 (25) 19 (12) 44 (28) 87 (56) 85 (55) 58 (37) 59 (35) 96 (58) 13 (8) 14 (8) 11 (7) 8 (5) 0 (0) 2 (1) 2 (1) RAM 28 (30) 38 (40) 24 (26) 16 (18) 56 (63) 68 (76) 21 (24) 80 (82) 73 (82) 56 (63) 32 (36) 40 (41) 53 (55) 97 (7) 4 (4) 5 (6) 2 (2) 8 (8) 1 (1) 1 (1) 2 (2) 5 (6) 7 (8) 4 (4) p-value 0.147 0.001 0.012 0.000 0.677 0.829 0.002

ARTIGO ORIGINAL 6 p = 0.00 4 analysis time 2 Kaplan-Meier Estimate Acta Med Port 2014 May-Jun;27(3):xxx-xxx May-Jun;27(3):xxx-xxx Port 2014 Acta Med Stages: I II III IV 0 We We observed a 5-year overall survival of 80% for This study reports a unique analysis of possible In this retrospective study, survival was substantially 1.00 0.75 0.25 0.00 0.50 Figure 2 - Survival by Stage, Kaplan-Meier options options by tumor stage, there was an association between stage and surgery, with less surgery being performed Stage III in (18%) and IV (2%), and an association between chemotherapy and tumor stage, with more chemotherapy treatment of Patterns (49%). patients II Stage to given being Regarding regions. geographical between different not were the time elapsed geographical all in between months 2.3 of interval similar diagnosis a registered and treatment we regions. Survival the population in the present study (Fig. 1). association There is between an survival and with a 5-year survival staging of 92% for patients (p presenting with = Stage I disease, 86% for Stage II, 0.00), 60% for Stage III and a for Kaplan-Meier plots 2). (Fig. IV Stage 20% for survival of overall survival by hormone receptor expression revealed an improved survival in the ER-positive group compared with the ER-negative group, and in the PR-positive group compared with the PR-negative group. phenotypes HR/HER2-triple tumor with accordingly survival When analyzing from survival decreasing progressive a found we 0.00), = (p the triple positive (ER-positive/PR-positive/HER2-positive) tumor sub-type ER- and ER-negative/PR-negative/HER2-positive to negative, the ER-positive/PR-positive/HER2- negative/PR-negative/HER2-negative (Fig. 3). There were for the studied geographical regions no survival differences (p = 0.7637) (Fig. 4). DISCUSSION geographical variations in breast cancer epidemiology and disclosure the Hence, Portugal. South across management of this information will support the further magnitude understanding of of unmet medical needs, the knowledge of high in risk regions for breast cancer parallel in the with southern territory of Portugal. inferior in patients with advanced disease, as of Geographical region triple-negative tumors. with patients well as in

4 6 4 analysis time R e v i s ta C i e n tífi c a d a Or d e m d o s M é d i c o s w w w.a c ta m e d i c a p o r tu g u e s a .c o m 2 Kaplan-Meier survival estimate Rosário André M, et al. Geographical variations in breast cancer epidemiology, epidemiology, breast cancer variations in Geographical M, et al. André Rosário 0 Eighty-eight percent of patients (1195 cases) were 1.00 0.75 0.25 0.00 0.50 Figure 1 - Overall Survival, Kaplan-Meier submitted to a in radical mastectomy and 46% in being performed surgery surgical procedure, with 42% of cases. Chemotherapy was administered to 53% of conservative patients, radiotherapy was performed in 61% and hormone therapy was given to 64% of patients. Looking at treatment Treatment patterns Treatment morphology morphology was Invasive Ductal Carcinoma accounting for 82.8% of all cases followed by Invasive Lobular Carcinoma As expected, (4.6%). Inflammatory Carcinoma represented only 0.4% of all cases. Staging distribution shows that 32% of patients presented with Stage I disease, 36% with Stage disease metastatic presented 6% and III Stage with 17% II, Analyzing ab initio. stage distribution by geographical area showed fewer Stage I patients (26%) in 49% information, status RAM. receptor hormone with patients For 181 the 1 (584) were both ER- and PR-positive, 15% (172) were ER- positive and PR-negative, 3% (34) were ER-negative and PR-positive, and 17% (199) were ER- and Mean PR-negative. age at diagnosis was 61 years for ER-positive and PR-positive, 61 years for ER-positive and PR-negative, 57 years for ER-negative and PR-positive, and 59 years for ER-negative and PR-negative. This was not significantly different (p = 0.082) by one-way analysis of variance joint for ER and PR profiles. HER2available for status1028 cases (76%), informationwith the was majority of them (796 cases, 77%) being HER2-negative. 23% The (232 remaining cases) had HER2-positive disease. Mean age at diagnosis was 61 for HER2-negative and 57 for HER2- profiles ER/PR/HER2 joint for analysis The disease. positive ER-positive/PR-positive/ of (48%) proportion high a revealed HER2-negative tumors. Twelve percent of triple-positive (ER-positive/PR-positive/HER2-positive), 6% tumors were presented as ER-negative/PR-negative/HER2-positive and 9% were triple negative (ER-negative/PR-negative/HER2- negative). We observed some significant differences in the geographical distribution of tumor profiles, withincidence of a higher triple-negative tumors in RAM and a incidence of triple-positive tumors in Algarve the compared higher with other regions.

ARTIGO ORIGINAL ewe rgos a b de o ifrne i acs to health care. access Also it has been in suggested by some studies differences to due be may regions between difference The RAM. in lower was disease stage early of more elderly the people in with rural areas. of regions, In our between study, knowledge distribution the incidence previous population Portuguese our with accordance in are Alentejo, in population aged an with regions, geographical residence didnotsubstantiallyaffect survival. aa ult ws eedn o te hruhes f data of and thoroughness the nature, on dependent was in quality data retrospective was study The limitations. the of sub-groups (e.g. RAM). We also recognize other significant some in small relatively equitable, is patients not of number is and region geographical by Nevertheless, distribution included. this the patients of of number strength the is main study The weaknesses. and strengths regions inourstudy. geographical Portuguese between survival evident in no differences for were there outcome Finally, group. worse triple-negative the and group patients HER2-positive showing a better outcome for the triple-positive HR-positive/ survival, for characteristics biological tumor of influence an in survival confirmed we addition, lower In disease. advanced and with patients disease localized with patients at 5years in survival a higher confirmed stage by analysis Survival status. HER2 evaluate to used methods assay the differences in reflect solely or diseases, distinct biologically these differences represent a truly geographical variation of whether clarify to completed be to need will studies Further RAM, the in tumors HER2-positive of number high a and Algarve. in tumors HER2-negative of status, incidence high HER2 a with considering when differences noticed we contrary,the On regions. among patterns expression tumor our study, we did not find differences in the incidence of HR ER-negative, as they respond better to hormone therapy. In are cancers breast known to correlate with ER-positive a better outcome than those areas. that are rural more the in responsible for these differences with less educated women present with early-stage breast cancer, and this can also be to likely more are education higher have who women that Figure 3-Survivalby Tumor HR/HER2phenotypes,Kaplan-Meier 0.50 0.00 0.25 0.75 1.00 ER+PR+HER2+ER+PR+HER2-ER-PR-HER2+ER-PR-HER2- h osre dfeecs n g dsrbto by distribution age in differences observed The Our results need to be considered in light of the study the of light in considered be to need results Our 0 Rosário André M,etal.Geographicalvariationsinbreastcancerepidemiology, Kaplan-Meier Estimate 2 ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R analysis time 4 p =0.00 6 11,12

5 Paula Gomes (Maternidade Alfredo da Costa), Victor Silva Victor Costa), da (Maternidade Alfredo Gomes Paula TerezaÉvora), de Santo TeresaEspírito (Hospital Timóteo Fernando Fonseca), Teresa Barreiros (Hospital do Montijo), (Centro (Hospital Santos Loureiro Sofia Baixo Alentejo), Hospitalar Barroso Sérgio Xavier), Ramos Francisco São Sância Hospital Abrantes), and Cruz Santa de de Hospital and Moniz Egas de Unidade (Hospital – Tejo Médio Nossa Senhora do Rosário), Rui Coelho (Centro Hospitalar Tejo – Unidade de Torres Novas), Rosa Madureira (Hospital Garcia de Orta), Osvaldo Francês (Centro Hospitalar Médio (Hospital Brito José Maria Santarém), de Distrital (Hospital Gloria Luísa CUF), (Hospitais Gouveia Joaquim de Setúbal), Hospitalar (Centro Gonçalves Isabel Vedras), de Torres Hospitalar (Centro Carvalho Isabel Faro), (Hospital de Furtado Distrital Irene Cascais), de Hospitalar (Centro Valadasbarlavento Oliveira do Helena Hospitalar Algarvio), (Centro Gabriela Central), Lisboa de Hospitalar (Centro Valente), Pulido Marcos Fernanda Cabral), Curry Hospital (Hospital Cunha Daniela – Norte Lisboa de Hospitalar (Centro (Centro Hospitalar do Funchal), Boto Carvalheira Santos (Centro Carlos Alentejano), Médio TejoHospitalar de Tomar),Unidade – Fraga Cláudia Litoral do (Hospital Aldeia Carlos Portalegre), de Hospital – Alentejano Norte do Saúde de Local (Unidade Lopes Principal), Artur Militar Lisboa Norte – Hospital de ), de Ana Paula Horta (Hospital Oncologia Lisboa de Hospitalar (Centro Palha Ana Gentil), de Francisco Ana Santos), Português dos (Instituto Reynaldo Miranda de (Hospital Alcazar Ana The ROR-SulWorking Groupconsistsof: ACKNOWLEDGEMENTS studied regions. geographical various the across patients cancer breast in differences survival of inexistence apparent the and types hormone sub- tumor of variation geographical stage, the regarding namely tumor and questions, important raises and status, HER2 and receptor survival patient between no-measurable and measurable confounders inourresults. of acknowledge effect we possible Also, the records. medical and collection Figure 4-SurvivalbyGeographicalRegion,Kaplan-Meier 0.50 0.00 0.25 0.75 1.00 In conclusion, our study confirms the association the confirms study our conclusion, In Alentejo Algarve LVT RAM 0 Acta MedPort2014May-Jun;27(3):xxx-xxx Kaplan-Meier Estimate 2 analysis time 4 p =0.76 6

ARTIGO ORIGINAL 2013 May 13] Available on: ] Available on: http://www.ine.pt Available y 13] Breast Cancer Res Treat. 2002;73:45–59. Treat. Breast Cancer Res ed. Geneva: WHO; 2000. rd Acta Med Port 2014 May-Jun;27(3):xxx-xxx May-Jun;27(3):xxx-xxx Port 2014 Acta Med http://www.ine.pt World Health Organization. International Classification of Diseases for 3 Oncology. Registo Oncológico Lisboa: 2006. ISM – Portugal de Sul Região na Cancro por Mortalidade Regional Sul. RORS; 2012. Incidência, Sobrevivência Bastos J, Barros H, e Lunet N. Evolução da mortalidade por cancro da Acta Med Port. 2007;20:139-44. mama em Portugal (1955-2002). Instituto Nacional de Estatística. Estatísticas INE; 2007. [Consulted in 2013 Ma Demográficas. Lisboa: Instituto Nacional de Estatística residente para o ano 2005, por . género e grupos etários, NUTS I, II, Estimativa III anual e Municípios da (NUTS 2002). [Consulted in população compared with white women. Arch Fam Med. 1999;8:521-8. compared with white women. carcinoma breast in disparities Racial HP. Freeman CA, Lamar KC, Chu survival rates: separating factors that affect diagnosis from factors that 2003;97:2853-60. treatment. Cancer. affect Bradley CJ, Given CW, Roberts C. Race, Socioeconomic Status, 2002;94:490- Inst. and Cancer Natl J Survival. and Treatment Cancer Breast 6. Elston Ellis CW, IO. Pathological prognostic factors in breast I. cancer. large a from experience cancer: breast in grade histological of value The 1991;19:403-10. study with long-term follow-up. Histopathology. Joslyn SA. Hormone receptors in breast cancer: racial distribution and survival. differences in International Union Against Cancer. TNM Classification of 6th ed.. Geneva: UICC; 2002. Tumours. Malignant The authors thank the Portuguese Ministry of Health for Health of Ministry Portuguese the thank authors The 19. 15. 16. 17. 18. 11. 12. 13. 14. 20. FUNDING SOURCES FUNDING the in role no had source funding The research. this funding study design, writing or this the paper, decision to submit it for publication. 6 et et al. Ries LA, Howe , HL et al. Wiggins CL, Brinton LA. Global Ward Ward E, . Global cancer Global D. Forman Smith R, Kang H, , Devesa SS, Howe HL, , Ward E, Ward Wallace AM, Wallace Cokkinides V Ferlay J, Ferlay R e v i s ta C i e n tífi c a d a Or d e m d o s M é d i c o s w w w.a c ta m e d i c a p o r tu g u e s a .c o m 2011;61:69-90. Wingo , PA Anderson WF Ward Ward E, Royce ME, Brown ML, Dozier JM, Rosário André M, et al. Geographical variations in breast cancer epidemiology, epidemiology, breast cancer variations in Geographical M, et al. André Rosário Jemal A, Nibbe A, Trends in breast cancer Trends by race and Cancer ethnicity: update 2006. CA J Clin. 2006;56:168-83. Hill DA, Method of detection and breast cancer survival disparities in Hispanic 2010;19:2453-60. women. Cancer Epidemiol Biomarkers Prev. women black of trends cancer Breast OW. Brawley RE, Tarone KC, Chu Ferlay J, Shin HR, GLOBOCAN 2008 Bray v1.2, Cancer F, incidence Forman IARC and D, CancerBase mortality worldwide: No. Mathers 10. C, Research on Cancer; 2010. Lyon, Parkin France: DM. International MM, Center Agency F, Bray A, Jemal for burden global the assess to statistics of Use LM. Fernandez DM, Parkin Breast J. 2006;12:S70–80. of breast cancer. Althuis MD, The authors declare that they have no conflicts of J Clin. Cancer statistics. CA trends in breast cancer Epidemiol. 2005;34:405-12. incidence and mortality Edwards 1973-1997. BK, Int J al. Annual report to the nation featuring on population-based the trends in status cancer of treatment. J cancer, Natl 1975-2002, Cancer Inst. 2005;97:1407-27. Levi F, Bosetti C, Lucchini F, Negri E, La decrease Vecchia C. in Monitoring breast the cancer mortality in 2005;14:497-502. Europe. Eur J Cancer Prev. Bosetti C, Bertuccio P, Levi F, Chatenoud L, Negri E, The La decline in Vecchia breast cancer C. mortality in Europe: An update (to 2009). Breast. 2012;21:77-82. Smigal C, 9. 10. 2. 3. 4. 1. interest. 5. CONFLICTS OF INTEREST CONFLICTS (Unidade (Unidade Local de Saúde do Norte Alentejano – Hospital de Elvas). REFERENCES 6. 7. 8.

ARTIGO ORIGINAL