{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:04:18Z","timestamp":1793131458994,"version":"4.5.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Breast Cancer Association","award":["."],"award-info":[{"award-number":["."]}]},{"name":"Visare Norr grant","award":["grant no: 750491"],"award-info":[{"award-number":["grant no: 750491"]}]},{"name":"The Department of Research and Development V\u00e4sternorrland County Council","award":["grant no: LVNFOU834391"],"award-info":[{"award-number":["grant no: LVNFOU834391"]}]},{"name":"The Percy Falk Foundation for medical research","award":["."],"award-info":[{"award-number":["."]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The Breast Cancer DataBase Sweden (BCBaSe) includes all women diagnosed with BC from 1992 to 2012 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200960,217) and age-matched women without a history of BC (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009300,791) in three Swedish health care regions. Information on comorbidity, educational level, and incidence of IHD was obtained through linkage with population-based registries. The risk of IHD was estimated by Cox proportional hazard regression analyses and cumulative incidence by the Kaplan-Meier method.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Women with BC had a lower risk of IHD compared to women without BC with a hazard ratio (HR) of 0.91 (95% CI 0.88\u20130.95). When women with left-sided BC were compared to right-sided BC, an increased HR for IHD of 1.09 (95% CI 1.01\u20131.17) was seen. In women receiving RT, a HR of 1.18 (95% CI 1.06\u20131.31) was seen in left-sided compared to right-sided BC, and the HRs increased with more extensive lymph node involvement and with the addition of systemic therapy. The cumulative IHD incidence was increased in women receiving left-sided RT compared to right-sided RT, starting from the first years after RT and sustained with longer follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Women given RT for left-sided BC during 1992 to 2012 had an increased risk of IHD compared to women treated for right-sided BC. These women were treated in the era of three-dimensional conformal RT (3DCRT), and the results emphasize the importance of further developing and implementing RT techniques that lower the cardiac doses, without compromising the beneficial effects of RT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13058-020-1249-2","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T11:02:55Z","timestamp":1579690975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Long-term risk of ischemic heart disease after adjuvant radiotherapy in breast cancer: results from a large population-based cohort"],"prefix":"10.1186","volume":"22","author":[{"given":"Anna-Karin","family":"Wennstig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"Wadsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Garmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Fredriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Blomqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Holmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greger","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Sund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,22]]},"reference":[{"issue":"2","key":"1249_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.radonc.2011.06.016","volume":"100","author":"P McGale","year":"2011","unstructured":"McGale P, Darby SC, Hall P, Adolfsson J, Bengtsson NO, Bennet AM, et al. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol. 2011;100(2):167\u201375.","journal-title":"Radiother Oncol"},{"issue":"11","key":"1249_CR2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa1209825","volume":"368","author":"SC Darby","year":"2013","unstructured":"Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987\u201398.","journal-title":"N Engl J Med"},{"issue":"11","key":"1249_CR3","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1200\/JCO.2016.69.8480","volume":"35","author":"VA van den Bogaard","year":"2017","unstructured":"van den Bogaard VA, Ta BD, van der Schaaf A, Bouma AB, Middag AM, Bantema-Joppe EJ, et al. Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures. J Clin Oncol. 2017;35(11):1171\u20138.","journal-title":"J Clin Oncol"},{"issue":"25","key":"1249_CR4","doi-asserted-by":"publisher","first-page":"4100","DOI":"10.1200\/JCO.2005.05.1037","volume":"24","author":"EE Harris","year":"2006","unstructured":"Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006;24(25):4100\u20136.","journal-title":"J Clin Oncol"},{"key":"1249_CR5","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1471-2407-7-9","volume":"7","author":"R Roychoudhuri","year":"2007","unstructured":"Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Moller H. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study. BMC Cancer. 2007;7:9.","journal-title":"BMC Cancer"},{"issue":"5","key":"1249_CR6","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1016\/j.ijrobp.2007.05.034","volume":"69","author":"CW Taylor","year":"2007","unstructured":"Taylor CW, Nisbet A, McGale P, Darby SC. Cardiac exposures in breast cancer radiotherapy: 1950s-1990s. Int J Radiat Oncol Biol Phys. 2007;69(5):1484\u201395.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"4","key":"1249_CR7","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1200\/JCO.2011.34.5900","volume":"30","author":"G Nilsson","year":"2012","unstructured":"Nilsson G, Holmberg L, Garmo H, Duvernoy O, Sjogren I, Lagerqvist B, et al. Distribution of coronary artery stenosis after radiation for breast cancer. J Clin Oncol. 2012;30(4):380\u20136.","journal-title":"J Clin Oncol"},{"key":"1249_CR8","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1200\/JCO.2006.08.6595","volume":"25","author":"CR Correa","year":"2007","unstructured":"Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ, Harris EE. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol. 2007;25:3031\u20137.","journal-title":"J Clin Oncol"},{"issue":"21","key":"1249_CR9","first-page":"3031","volume":"25","author":"CW Taylor","year":"2007","unstructured":"Taylor CW, Povall JM, McGale P, Nisbet A, Dodwell D, Smith JT, et al. Cardiac dose from tangential breast cancer radiotherapy in the year 2006. Int J Radiat Oncol Biol Phys. 2007;25(21):3031\u20137.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"1249_CR10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.radonc.2016.11.007","volume":"122","author":"AK Wennstig","year":"2017","unstructured":"Wennstig AK, Garmo H, Hallstrom P, Nystrom PW, Edlund P, Blomqvist C, et al. Inter-observer variation in delineating the coronary arteries as organs at risk. Radiother Oncol. 2017;122(1):72\u20138.","journal-title":"Radiother Oncol"},{"issue":"15","key":"1249_CR11","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1200\/JCO.2016.72.0722","volume":"35","author":"C Taylor","year":"2017","unstructured":"Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J, et al. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol. 2017;35(15):1641\u20139.","journal-title":"J Clin Oncol"},{"key":"1249_CR12","doi-asserted-by":"crossref","unstructured":"Goldvaser H, Barnes TA, Seruga B, Cescon DW, Ocana A, Ribnikar D, et al. Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(1):31-9.","DOI":"10.1093\/jnci\/djx141"},{"issue":"3","key":"1249_CR13","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1093\/annonc\/mdw673","volume":"28","author":"F Khosrow-Khavar","year":"2017","unstructured":"Khosrow-Khavar F, Filion KB, Al-Qurashi S, Torabi N, Bouganim N, Suissa S, et al. Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2017;28(3):487\u201396.","journal-title":"Ann Oncol"},{"issue":"12","key":"1249_CR14","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1056\/NEJMcibr1214975","volume":"368","author":"DB Sawyer","year":"2013","unstructured":"Sawyer DB. Anthracyclines and heart failure. N Engl J Med. 2013;368(12):1154\u20136.","journal-title":"N Engl J Med"},{"issue":"15","key":"1249_CR15","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1093\/jnci\/djn206","volume":"100","author":"M Ryberg","year":"2008","unstructured":"Ryberg M, Nielsen D, Cortese G, Nielsen G, Skovsgaard T, Andersen PK. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100(15):1058\u201367.","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"1249_CR16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.radonc.2017.03.012","volume":"123","author":"JC Rehammar","year":"2017","unstructured":"Rehammar JC, Jensen MB, McGale P, Lorenzen EL, Taylor C, Darby SC, et al. Risk of heart disease in relation to radiotherapy and chemotherapy with anthracyclines among 19,464 breast cancer patients in Denmark, 1977-2005. Radiother Oncol. 2017;123(2):299\u2013305.","journal-title":"Radiother Oncol"},{"issue":"4","key":"1249_CR17","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/s41416-018-0159-x","volume":"119","author":"NB Boekel","year":"2018","unstructured":"Boekel NB, Jacobse JN, Schaapveld M, Hooning MJ, Gietema JA, Duane FK, et al. Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer. Br J Cancer. 2018;119(4):408\u201318.","journal-title":"Br J Cancer"},{"key":"1249_CR18","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/1471-2458-11-450","volume":"11","author":"JF Ludvigsson","year":"2011","unstructured":"Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.","journal-title":"BMC Public Health"},{"key":"1249_CR19","unstructured":"Statistiska centralbyr\u00e5n: Longitudinell integrationsdatabas f\u00f6r sjukf\u00f6rs\u00e4krings- och arbetsmarknadsstudier (LISA) http:\/\/www.scb.se\/vara-tjanster\/bestalla-mikrodata\/vilka-mikrodata-finns\/longitudinella-register\/longitudinell-integrationsdatabas-for-sjukforsakrings%2D%2Doch-arbetsmarknadsstudier-lisa\/. Accessed July 11, 2019."},{"issue":"5","key":"1249_CR20","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373\u201383.","journal-title":"J Chronic Dis"},{"key":"1249_CR21","unstructured":"R Core Team: R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2018 https:\/\/www.R-project.org\/. Accessed July 11, 2019."},{"issue":"4","key":"1249_CR22","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1002\/cncr.22452","volume":"109","author":"R Jagsi","year":"2007","unstructured":"Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ. Rates of myocardial infarction and coronary artery disease and risk factors in patients treated with radiation therapy for early-stage breast cancer. Cancer. 2007;109(4):650\u20137.","journal-title":"Cancer."},{"issue":"1","key":"1249_CR23","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/cncr.11467","volume":"98","author":"EB Lamont","year":"2003","unstructured":"Lamont EB, Christakis NA, Lauderdale DS. Favorable cardiac risk among elderly breast carcinoma survivors. Cancer. 2003;98(1):2\u201310.","journal-title":"Cancer."},{"key":"1249_CR24","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.ypmed.2015.09.011","volume":"81","author":"G Damiani","year":"2015","unstructured":"Damiani G, Basso D, Acampora A, Bianchi CB, Silvestrini G, Frisicale EM, et al. The impact of level of education on adherence to breast and cervical cancer screening: evidence from a systematic review and meta-analysis. Prev Med. 2015;81:281\u20139.","journal-title":"Prev Med"},{"issue":"5","key":"1249_CR25","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1097\/SLA.0000000000002239","volume":"267","author":"LE Elshof","year":"2018","unstructured":"Elshof LE, Schmidt MK, Rutgers EJT, van Leeuwen FE, Wesseling J, Schaapveld M. Cause-specific mortality in a population-based cohort of 9799 women treated for ductal carcinoma in situ. Ann Surg. 2018;267(5):952\u20138.","journal-title":"Ann Surg"},{"issue":"8","key":"1249_CR26","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1080\/0284186X.2016.1182209","volume":"55","author":"G Nilsson","year":"2016","unstructured":"Nilsson G, Witt Nystrom P, Isacsson U, Garmo H, Duvernoy O, Sjogren I, et al. Radiation dose distribution in coronary arteries in breast cancer radiotherapy. Acta Oncol. 2016;55(8):959\u201363.","journal-title":"Acta Oncol"},{"issue":"1","key":"1249_CR27","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13014-019-1242-z","volume":"14","author":"AK Wennstig","year":"2019","unstructured":"Wennstig AK, Garmo H, Isacsson U, Gagliardi G, Rintela N, Lagerqvist B, et al. The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol. 2019;14(1):40.","journal-title":"Radiat Oncol"},{"key":"1249_CR28","unstructured":"Lancet. 2005;365(9472):Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials, 1687\u2013717."},{"issue":"17","key":"1249_CR29","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1093\/jnci\/djr242","volume":"103","author":"E Amir","year":"2011","unstructured":"Amir E, Seruga B, Niraula S, Carlsson L, Ocana A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299\u2013309.","journal-title":"J Natl Cancer Inst"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-020-1249-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13058-020-1249-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-020-1249-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T19:11:25Z","timestamp":1611169885000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/s13058-020-1249-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,22]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1249"],"URL":"https:\/\/doi.org\/10.1186\/s13058-020-1249-2","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,22]]},"assertion":[{"value":"30 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures performed in this study involving human participants were in accordance with the ethical standards of the regional committee of ethics in Stockholm, reference number 2013\/1272-31\/4 and with the 164 Helsinki Declaration and its later amendments or comparable ethical standards.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10"}}