Breast Cancer Incidence and the Air Pollution Level in the Communes of Chile: an Ecological Study

Breast cancer incidence and the air pollution level in the communes of Chile: an ecological study

Jorge Sapunar Zenteno1,2,3, Pedro Ferrer Rosende1, Badir Chahuán Manzur3 and Isabel Saffie Vega3

1Epidemiology Research Unit, Research Department, Instituto Oncológico Fundación Arturo López Pérez, Cano y Aponte 927, Providencia, Santiago 7500000, Chile 2EPICYN Center, Department of Internal Medicine, Facultad de Medicina, Universidad de La Frontera, Temuco 4780000, Chile 3Breast Oncology Surgery Unit, Instituto Oncológico Fundación Arturo López Pérez, Santiago 7500000, Chile

Abstract

There is evidence linking air pollutants associated with vehicular traffic such as poly- cyclic aromatic hydrocarbons with breast carcinogenesis. Epidemiological studies have shown conflicting results regarding air pollution and breast cancer risk, which could be explained by the multitude of other risk factors that could affect the association. In Chile, air pollution has reached alarming levels, either due to motorised vehicle traffic or the combustion of wood for heating; therefore, our objective was to evaluate the association between the incidence of breast cancer and the concentration of the main air pollutants monitored in the country. Research We carried out a cross-sectional ecological study that evaluated the association between the average incidence of breast cancer in years (2016 to 2018) and the average annual concentration of six atmospheric pollutants in the 5 years prior to the estimation of the rate in communes of Chile, using the population of beneficiaries of Instituto Oncológico Fundación Arturo López Pérez. The annual incidence of breast cancer was 72.21 cases per 100,000 women and it varied significantly in the communes studied compared to the human development index (HDI) and to the proportion of women in the age group at highest risk. Assessing the relationship between the incidence of breast cancer and the average concentration of atmospheric pollutants, we only found a direct correlation between the level of nitrogen dioxide and the rate (R = 0.82; p = 0.044), whose sig- Correspondence to: Jorge Sapunar Zenteno nificance tends to be lost when age and the communal HDI are included in a regression Email: [email protected] model. ecancer 2021, 15:1191 https://doi.org/10.3332/ecancer.2021.1191 Keywords: breast cancer, epidemiology, air environmental pollutants Published: 25/02/2021 Received: 08/07/2020 Publication costs for this article were supported by ecancer (UK Charity number 1176307). Introduction Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access Breast cancer is the leading cause of mortality attributed to malignant neoplasms in article distributed under the terms of the female population of Chile (15.59 deaths per 100,000 women per year) and it is also Creative Commons Attribution License (http:// creativecommons.org/licenses/by/3.0), which the most common cancer diagnosed in women in developed countries [1, 2]. The World permits unrestricted use, distribution, and Health Organization estimates that its incidence and mortality will move higher, forecast- reproduction in any medium, provided the original ing 3 million new cases of breast cancer worldwide in 2030 and 900,000 deaths from this work is properly cited.

ecancer 2021, 15:1191; www.ecancer.org; DOI: https://doi.org/10.3332/ecancer.2021.1191 1 pollutants monitored inChilethrough anecological study. Our objective was to evaluate whether there is an association between the incidence of breast cancer and the concentration of the main air due to motorised vehicle traffic or theburningof wood for heating [16]. industrypower andthermoelectric generation generate pollution. There are citiesin which air hasreached pollution alarminglevels, either Chile hasanetwork of air quality monitoring stationslocated inthemaincitiesor inplaces where productive asmining,heavy activitiessuch and thelarge number of other factors riskof breast cancer involved. risk ofthe incidentbreast cancer or mortality have hadcontradictory resultsdue to [11–15],inpart their design,thetypeof pollutantstudied also suggesting anoestrogenic effecton air pollution ciationhas beendemonstrated between exposure to respirable particulate matter2.5) andozone 2.5(PM (O3) higherwith mammary density, disruptorscrine or carcinogens. PAHs have anoestrogeniceffect and induce mammary tumours inanimalmodels[7,8].In anasso- humans, lung cancer, hasgainedincreasing interest. Polluted air contains polycyclic aromatic hydrocarbons (PAHs) andmetals that canactasendo- In oncology, environmental and in particular pollution atmospheric pollution, which is a known risk factor for of some types cancer as such hormonal therapies, amongothers [6]. the presence of relatives a diagnosisofwith breast cancer after 60 years, disorders nutritional dueto excess alcohol intake andexposure to of amalerelative breastwith cancer as wellirradiation aschest prior to age 30dueto other oncological diseases.Minor riskfactors are age, ian andbreast cancer, breast cancer diagnosedbefore theage of 50despite not having demonstrated pathogenic mutations, thepresence mutations carriage intheBRCA 1andBRCA 2genes stoodhaving out, first-and second-degree relatives with bilateral breast cancer, ovar minor factors according to whether they increaserisk of the disease more the or lessthan2times. Among themajor riskfactors, pathogenic not modifiablesuchasage, sex, age atfamily menopause, andpersonal history of breast cancer [5]. They canalsobeclassifiedasmajor and and ahigh-fat diet, alcohol andtobacco consumption, exposure to ionisingradiation inthechestandreproductive history. Other factors are factors for breast cancer, there areas theuseofones such modifiable contraceptives andhormonereplacement therapy, status nutritional gesterone receptorstumour, inthe statushormonal the of patient the and theinvasive nature orof insitu thedisease[4,5]. Among therisk Breast cancer isaheterogeneous diseaseandtherefore theassociated riskfactors vary according to theexpression of oestrogen andpro - tion. cause ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 To correctthe estimation was performed for female sex andonly breast cancer casesinbeneficiaries of theoncology agreement were considered. oncology agreement was obtained, as well asthenew cases of breast cancer treated at theInstitute in2016,2017and2018. The Incidence With theapproval of theScientificEthics Committee of theFALP, by thedistribution age, sex andcommune of thebeneficiaries of the oncological agreement. possibilityhas the tion of contractingan agreement for coverage of diagnosticbenefits andtreatment events,against neoplastic calledan selected. The Instituto Oncológico Fundación Arturo López Pérez (FALP)meets thesecharacteristics. The population cared for inthisinstitu- In order to obtain thestudy population, a healthcentre inChile focused oncancer management andthat hasacaptive population was and theaverage annualconcentration of the5 years prior to estimated incidence of sixair pollutants incommunes of Chile. An ecologicalcross-sectional study thatevaluated association the between average incidence of breast cancer in3 years (2016,2017,2018) Subjects and methods (NO distributed in Chile. The pollutants studied were respirable PM2.5,10, sulphur dioxide (SO The average annualconcentration of atmosphericpollutants was basedondata records obtained from theair quality monitoring stations Chilean population, thisrate was adjusted by age distributionfrom 2012census usingthedirect method. 2 ) andozone (0 [3]. It isessential to recognise thefactors associated the riskandprognosiswith of thisdiseasefor itsprimary andsecondary preven- potentialinherent 3 ). The techniquesto determinethe concentration of atmospheric pollutants are available onthe website of theNational bias projectingincidencethe of breast cancer from thepopulation intheFALP oncology agreement to the [9, 10].Some studies that have investigated the association between air and pollution 2 ), nitrogen monoxide (NO), nitrogen dioxide 2 -

Research level andtherate (R=0.82;p0.044). ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 concentration of atmosphericpollutants between the yearsthe direct 2011and2015,ruling out andsignificant correlation between theNO Figure 3shows thecorrelationbetween theaverage adjusted incidence of breast cancer between the years 2016and2018theaverage found adirect andsignificant correlation (R=0.68 the Los Lagos Region (Table 2).By evaluating therelationshipbetween theadjusted incidence of breast cancer andthecommunal HDI, we per100 cases than 100,000. The lowestrates are Temuco inthe Araucanía Region, LaSerena intheCoquimbo Region andPuerto Montt in agreement, LasCondes, Puente Alto, La Florida in the Metropolitan Region and Viña del Mar in Valparaíso region stand out, with rates greater By comparing the adjusted incidence of breast cancer among the 14 communes with more than 5,000 beneficiaries of the FALP oncology Figure 1shows theage distributionof breast cancer cases,concentrating mostof thesebetween 45and65 years (57.5%). women inoncology agreement per year was 80.9,70.3and64.9in2016,20172018,respectively (Table 1). in theagreement was 275,768,310,162and339,096in2016,20172018,respectively. The incidence of breast cancer per 100,000 During the2016–2018period,661new casesof breast cancer were treated in women with anoncology agreement. The female population Results variable, considering age andHDIby commune. significant.Finally, linearmultiple using regression, we evaluated theeffect of air ontheincidence pollution of breast cancer asadependent in theage groupat risk for breastcancer was analysedPearson’s using correlation coefficient. A p-value <0.05 was considered statistically dence of cancer the averagewith concentration of contaminants,and theproportion theHDI of beneficiaries of theoncology agreement Statisticalanalysis was performed programR the with version 3.6.0(RCore Team, 2018. Vienna, Austria). The correlation between theinci- stations and validated records. munes a femalewith population of beneficiariesin anoncology agreement greater than5,000peopleandthat will have active monitoring To evaluateassociation the between incidence the of breastcancer andtheaverage concentration of air pollutants, we selected thosecom- development index (HDI),thisindicator was obtained by commune [18]. [13, 14], we obtained theindex of motorised vehicles perby capita commune [17].By theassociation between cancer incidence andhuman Considering that theliterature recognises anassociation between theriskof breast cancer andpollutants linked to motor vehicle traffic of validated data intheoldestrecords. Air Quality Information System (SINCA) b a adjusted incidence according to projections of the2012census. Table 1.Beneficiary population of theFALP oncology agreement inthe years 2016,2017and2018,average age anddirect age- (F According to census projections 2012 Average age of cases(range) Female population oncological agreement Cases Incidence by per 100,000(CI Age-adjusted incidence (CI (2,662) = 1.86;p0.157) 95% a 95% ) b ) [16]. The average of thelast5 years prior to theincidence estimate was considered dueto thelack p =0.007)(Figure 2). 80.9 (70.6,92.2) 82.6 (69.5,97.5) 55.8 (24–87) 275,768 2016 223 70.3 (61.3,80.3) 70.2 (59.6,82.1) 54.6 (27–88) 310,162 2017 218 64.9 (56.6,74.0) 71.2 (59.8,84.1) 56.8 (26–88) 339,096 2018 220 3 2

Research ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 borough asadependent variable inalinear regression modelthat includesthe variables age(Table andHDI 3). The association tendswith NO2 to belost when analysing theeffect of thelevel of thesixair pollutants ontheincidence of breast cancer by Figure 1.Distribution by age group of breast cancer casesin women beneficiaries of the FALP oncology agreement between 2016and2018. 2018, age adjusted riskgroup. Table 2.Beneficiary population of theFALP oncology agreement by commune andbreast cancer incidence for the years 2016,2017and Viña delMar Temuco Talca Santiago Punta Arenas Puerto Montt Puente Alto Los Angeles Las Condes La Serena La Florida Concepción Chillán Antofagasta Commune Valparaíso La Araucanía Maule Metropolitana Magallanes Los Lagos Metropolitana Biobío Metropolitana Coquimbo Metropolitana Biobio Ñuble Antofagasta Region Adjusted incidence 150.7 (75.1,269.8) 114.1 (54.7,209.8) 106.5 (39.1,231.8) 132.4 (57.1,261.3) 77.6 (21.1,198.9) 85.7 (34.4,176.5) 76.5 (24.8,178.5) 97.9 (41.9,194.2) 49.3 (15.9,115.5) 38.1 (4.6,137.7) 20.4 (0.5,113.9) 62.3 (17,159.5) 71.5 (19.5,183) 16.6 (0.4,92.4) 2016 Adjusted incidence 124.3 (61.5,223.7) 181 (105.4,289.8) 84.6 (31.1,184.2) 98.7 (45.1,187.4) 66.5 (18.1,170.3) 55.4 (11.4,161.9) 73.8 (23.9,172.2) 73.2 (31.6,144.2) 36.4 (4.4,131.5) 37.9 (7.8,111.2) 98.3 (36,214.2) 48.7 (10,142.4) 14.7 (0.4,81.8) 92.8 (40,183) 2017 Adjusted incidence 124.9 (53.8,246.5) 104.6 (38.4,227.6) 80.6 (29.6,175.4) 62.2 (22.8,135.3) 77.1 (30.9,159.2) 79.5 (25.8,185.5) 80.8 (29.6,175.9) 55.9 (22.4,115.3) 53.5 (14.6,137) 168 (96,272.8) 105 (50,193.9) 13.2 (0.3,73.5) 15.4 (0.4,85.9) 43.4 (8.9,127) 2018 Adjusted incidence per 2016–2018 100,000 100.3 106.9 154.3 109.1 28.2 42.5 30.4 75.8 82.2 72.5 95.7 59.5 59.7 66.2 4

Research ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 2016 and2018by commune andage-adjusted riskstratum. Figure 3.Relationship between average levels of sixair pollutants between the years 2011and2015the average incidence of breast cancer between age adjusted riskstratum. Figure 2.Relationship between theHDIin2017and average incidence of breast cancer per 100,000peoplebetween 2016and2018 by commune and 5

Research that thedisease(breast cancer) didnot exist prior to exposure, isalimitationwhich of allstudiesof cross-section. Althoughconcentrationthe of contaminants was anaverage of the5 years prior to theestimation of theincidence, itcannot beguaranteed limitation of the study since it isnot possibleto know if the frequency of other risk factors is comparable between the communes studied. association onthe and HDI between levels of atmosphericpollutants andcommunity incidence of theneoplasia. This constitutes themain characterisationthe of population this in relation to risk factors for breast cancer isincomplete, beingonly ableto analyzsthe effect of age Subjectsand Methods the oncology section, agreement isacollective planfor companies. Our study ispopulation-based andunfortunately disease inrelationthe to general the population.However, rate the found issimilar to thatproposed by GLOBOCAN beneficiariesof theoncology agreement,since they couldhave hired itbecausethey have riskfactors for cancer, increasing theincidence of for highlevels of NO it didnot reach statisticalsignificance. The Sister cohort study intheUnited States reported anincreased riskof carcinoma ductal insitu regression model that considers other risk factors. According to SINCA [16] NO ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 5 ous years, we foundan association concentrationthe with of NO By evaluatingcorrelationthe between incidence the of breastcancer andtheaverage annualconcentration of sixair pollutants intheprevi- Araucanía Region to 154.2casesper 100,000 women per year inLasCondes, Metropolitan Region. great variation in the average annualised incidence of breast cancer that ranges from 28.8 cases per 100,000 women per year in Temuco, La areple, distributed throughoutcountrythe andhave importantgeographic andsocio-economic differences (Table 4 ). In them, we observe a The 14communesselected for analysis, considering apopulationof beneficiaries of theFALP oncology agreement greater than 5,000peo- ogy agreement ismostly acquired by companiesfor their workers, which would reduce theriskof selectionbiasgiven by individualaffiliation. partially corrected byratethe adjusting forage the of distribution thefemale population from the2012census. On theother hand,theoncol- demographicdifferences betweenpopulation the of womenin theFALP oncology agreement andthepopulation of Chilean women were per 100,000 women per year, afigure intherange observed for countries intheGLOBOCANwith ahighHDI projections. The possible Antofagasta) per 100,000 for theperiod2003–2007in the Province of Bío-Bío and31.0casesper 100,000 in theperiod1998–2002Region of centresper (33.1and33.3 cases 100,000forperiods 2001–2005and2006–2008,respectively, the intheRegion of Los Ríos, 30.4cases year women per year incountries and lowmedium with For HDI. South America, theGLOBOCAN estimate is56.8casesper 100,000 women per wide. The average incidence ofper thisdiseaseis54.4cases 100,000 women per year incountries and31.3casesperwith highHDI 100,000 According to Global Observatory of Cancer (GLOBOCAN)estimates, breastcancer accounts for 24.2%of new cancer casesin women world- Discussion that combined with volatile organic compoundsin the presence of sunlight forms O Canada, had established an associationCanada, hadestablished between NO of NO of of acidrain andincreasing thelevels of2.5. 10 andPM PM The commune of LasCondes exhibits thehighestaverage annualconcentrations resultssince the communesthat did not register NO smaller conurbations itislimited to contaminants previously recognised ascritical. The direction of thisbias would possibly not affect the thatare of part thelargestconurbations in Chile(Santiago, Valparaíso andConcepción), theregistry iscomplete, while incommunes of One oflimitations the of our studyoflack isthe validated records of allpollutants intheair quality monitoring stations. In thosecommunes incidence of breast cancer. in theRegion of La Araucanía,has highlevels of contamination by PM2.5attributable to thecombustion of firewood for heating alow but marker of motor vehicle traffic,being thepollutants associated with breast carcinogenesis PAHsofcommune Temuco, andmetals [7].The [2]. In incidencenon-annualised Chile,the rates of breastcancer available are only projections of thecasesregistered inthree sentinel 2 andhasthehighestadjusted average annualincidence of breast cancer. In thecaseof O [19]. Our study is thefirst inChile to obtain abreast cancer incidence rate for a population of women and this was 72.21cases 2 andfor invasive carcinomaonly statessouthern inthe [14].Previously, acase–control study conducted inMontreal, 2 have low incidences of breast cancer. There is alsothepossibility of selectionbiasinthe 2 contamination andinvasive breastcancer [13].In thesestudies,NO 2 that however losesstatistical significance linearwhen usingamultiple 2 is produced by theburningof at fuels high temperatures 3 and by doing with water contributes to the production 3 , we observed anRcoefficient of 0.61but [2] andasexplained in 2 was usedas a 6

Research ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 None. Conflicts of interest other riskfactors andestablish thetemporality of theassociation between exposure to air pollutants andincidence of breast cancer. by considering theeffectof variablesas age such New andHDI. studiesare required whose designmakes itpossibleto evaluate theeffect of relation between thefrequency of breast cancer andanair pollutant mainly related to motor vehicle traffic; however, this association islost In conclusion, the incidence of breast cancer in thestudiedpopulation is similar to that of countries high and HDI therewith is a direct cor Conclusion SE: standard error; PM:respirable particulate matter Table 3.Linear regression analysis for thepollutants effect onthebreast cancer incidence. NO PM PM O NO SO 3 2 2.5 10 2 Pollutant Table 4.Geographic anddemographic characteristics of the14communes of Chileincludedinthestudy. SL: southlatitude; mASL:meters above sealevel Viña delMar Temuco Talca Santiago Punta Arenas Puerto Montt Puente Alto Los Ángeles Las Condes La Serena La Florida Concepción Chillán Antofagasta Commune −0.27 (1.72) −0.09 (1.09) 4.94 (26.35) 0.46 (0.85) 5.51 (3.30) 3.85 (1.29) β (SE) Notadjusted value Valparaíso La Araucanía Maule Metropolitana Magallanes Los Lagos Metropolitana Biobío Metropolitana Coquimbo Metropolitana Bíobío Ñuble Antofagasta p-value 0.885 0.041 0.938 0.600 0.156 0.869 Region −0.08 (1.78) −0.26 (0.77) 0.30 (0.66) 4.18 (3.20) 5.14 (37.2) 3.45 (1.90) β (SE) Age adjusted value Age Latitude (SL) 33°01′ 38°44′ 35°25′ 33°27′ 53°28′ 41°28′ 33°37′ 37°28′ 33°25′ 29°54′ 33°33′ 36°38′ 36°36′ 23°38′ p-value 0.968 0.742 0.664 0.262 0.167 0.912 Altitude (m ASL) Altitude Adjusted value by population at risk −0.24 (2.16) −0.40 (0.97) 11.76 (12.1) 122 102 579 698 139 709 784 124 0.12 (0.87) 5.98 (3.64) 3.85 (1.50) 10 14 28 12 40 2 β (SE) Population 334.248 282.415 220.357 404.495 131.592 245.902 625.501 202.331 294.838 249.656 366.916 223.574 184.739 425.725 p-value 0.921 0.688 0.892 0.176 0.082 0.509 −0.16 (1.28) −0.02 (0.71) 0.681 (3.95) −1.77 (41.1) 0.17 (0.86) 2.13 (2.51) Adjusted value by HDI β (SE) 0.726 0.600 0.576 0.733 0.619 0.551 0.636 0.535 0.972 0.619 0.722 0.625 0.539 0.627 HDI p-value 0.912 0.846 0.460 0.976 0.871 0.973 7 -

Research 19. 18. 17. 16. 15. 14. 13. 12. 11. 10. 3. ecancer 2021, 15:1191; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1191 References None. Funding statement 9. 8. 7. 6. 5. 4. 2. 1. Prieto M(2011)Epidemiología del cáncer demama enChile http://www.ochisap.cl/images/SocioEconominoSaludComunas.pdf https://www.ine.cl/estadisticas/economia/transporte-y-comunicaciones/permiso-de-circulacion/parque-de-vehiculos https://sinca.mma.gob.cl/ Health Res 2212–21https://doi.org/10.1080/09603123.2011.588321 Wei Y, Davis J, andBina WF (2012)Ambient airassociatedis pollution with theincrease incidence of breast cáncer inUS Sutdy: aUS-Wide Cohort White AJ, Keller JP, andZhao S, lution inMontreal, Canada:acase-control study Crouse DL,Goldberg MS, and Ross NA, etal(2010) Environ Heath study cohort Garcíaa E,Hurleyteachers: California in S,andONelsoncáncerbreastrisk D, and et al (2015)Hazardouspollutantsair the Danish Nurse Cohort study Andersen ZJ, Ravnskjær L,and Andersen KK,et al (2017) Cancer Surveilance Consortium Yaghjyan L, Arao R,andBrokampC, et al (2017) Association between air pollutionandmammographic breast density intheBreast in theDanish diet, cancer andhealthcohort densityHuynhS, mammographic vonand Euler-Chelpinpollution airand Raaschou-NielsenM, O,toexposure etterm al (2015)Long ByrneC, Divekar SD, andStorchanGB, cancer incidence Environ Int 90185–192https://doi.org/10.1016/j.envint.2016.02.009 breast and hydrocarbons aromatic polycyclic of sourcesWhite AJ, Bradshaw multiple PT,to andHerring AH, et al (2016)Exposure org/10.1007/s10911-013-9273-9 Cancer Prev 183201–3206PMID: Nindrea R, Aryandono T, andLazuardi L (2017)Breastcancer factors risk among women inSoutheast ameta-analysisAsia: Natl Cancer Inst 8976–82https://doi.org/10.1093/jnci/89.1.76 PMID:8978410 Barclay J, Ernster V, andKerlikowske K,et al(1997)Comparisonof factors risk for ductalcarcinoma insituandinvasive breast cancer PMCID: Polyak K (2011) https://www.who.int/topics/cancer/breastcancer/es/index1.html worldwide for 36cancers in185countries CA Cancer J Clin Bray F, Ferlay J, andSoerjomataram,I, et al(2018)Globalcancer statistics 2018:GLOBOCAN estimates of incidence andmortality 106–114 https://doi.org/10.4067/S0034-98872017000100014 Icaza G,Núñez L,andBugueño H(2017)Epidemiologicalanalysis of breast cancer mortality in women inChile 3195489 1414–28https://doi.org/10.1186/1476-069X-14-14 eeoeet i bes cáncer breast in Heterogeneity Environ Health Prespect Cancer Epidemiol Biomarkers Prev 26428–430 https://doi.org/10.1158/1055-9965.EPI-16-0578 BCR etal (2019)Air clustering pollution, of particulate matter components, andbreast cáncer intheSister PMID: 29281867 PMCID: 1936–46https://doi.org/10.1186/s13058-017-0828-3 PMID:28381271 PMCID:5382391 et al(2013)Metalsand breast cancer 23338949 PMCID: Environ Health Environ Health Prespect 1181578–1583https://doi.org/10.1289/ehp.1002221 127https://doi.org/10.1289/EHP5131 J ClinInvest Postmenopausal breast cáncer is associated with exposure to traffic-related air pol- 5980871 Long-term exposure to fine particulate matter and breast cancer incidence in 1431–38https://doi.org/10.1186/s12940-015-0017-8 68394–424https://doi.org/10.3322/caac.21492 PMID:30207593 Rev Med ClinCondes 22428–443 4017651 121 3786–3788 J Mammary Gland Biol Neoplasia https://doi.org/10.1172/JCI60534 PMID: 21965334 18 63–73https://doi. Rev Med Chile

Int J EnvironInt J Asian PacAsian J 145 8 J

Research