{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:21:35Z","timestamp":1789399295879,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"F\u00e9d\u00e9ration Fran\u00e7aise de Cardiologie (FFC)","award":["755523"],"award-info":[{"award-number":["755523"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Background\u2014Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods\u2014The study included 101 left- or right-sided BC patients treated with RT without chemotherapy. A coronary CT angiography was performed before and 2 years after RT. Plaque development thorough the entire coronary network was defined as an increased number of plaques. Cardiac exposure was quantified with mean doses to the heart, left ventricle, and coronary arteries. Logistic regression models were used to assess association with doses. Results\u2014At inclusion, 37% of patients had plaques, increasing to 42% two years after RT. Overall plaque development was observed in seven patients: five with calcified plaque development and four with non-calcified plaque development. The risk of overall plaque development was significantly associated with doses to the Left Main and Circumflex coronary arteries (OR at 1 Gy = 2.32, p = 0.03 and OR at 1 Gy = 2.27, p = 0.03, respectively). Specific analyses for calcified and non-calcified plaque development showed similar results. Conclusion\u2014Our study suggests an association between coronary arteries exposure and the risk of developing both calcified and non-calcified atherosclerotic plaques over 2 years after BC RT. Trial registration number: NCT02605512.<\/jats:p>","DOI":"10.3390\/jcdd10070299","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:52:25Z","timestamp":1689213145000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Early Development of Atherosclerotic Plaques in the Coronary Arteries after Radiotherapy for Breast Cancer (BACCARAT Study)"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-0309","authenticated-orcid":false,"given":"Manoj Kumar","family":"Honaryar","sequence":"first","affiliation":[{"name":"INSERM U 1018, CESP, Radiation Epidemiology Team, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1895-8415","authenticated-orcid":false,"given":"Rodrigue","family":"Allodji","sequence":"additional","affiliation":[{"name":"INSERM U 1018, CESP, Radiation Epidemiology Team, 94800 Villejuif, France"},{"name":"Gustave Roussy, Research Department, 94800 Villejuif, France"},{"name":"University Paris-Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology (Oncorad), Clinique Pasteur, 31076 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-2111","authenticated-orcid":false,"given":"Mathieu","family":"Lapeyre","sequence":"additional","affiliation":[{"name":"Department of Radiology, Clinique Pasteur, 31076 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loic","family":"Panh","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Clinique Pasteur, 31076 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Camilleri","sequence":"additional","affiliation":[{"name":"Department of Radiology, Clinique Pasteur, 31076 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Broggio","sequence":"additional","affiliation":[{"name":"Department of Dosimetry, PSE-SANTE\/SDOS\/LEDI, Institute for Radiation Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6144-1297","authenticated-orcid":false,"given":"Jean","family":"Ferri\u00e8res","sequence":"additional","affiliation":[{"name":"Department of Cardiology and INSERM UMR 1295, Rangueil University Hospital, 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8374-9281","authenticated-orcid":false,"given":"Florent","family":"De Vathaire","sequence":"additional","affiliation":[{"name":"INSERM U 1018, CESP, Radiation Epidemiology Team, 94800 Villejuif, France"},{"name":"Gustave Roussy, Research Department, 94800 Villejuif, France"},{"name":"University Paris-Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Jacob","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology, PSE-SANTE\/SESANE\/LEPID, Institute for Radiation Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrc3007","article-title":"Strategies to improve radiotherapy with targeted drugs","volume":"11","author":"Begg","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/cncr.21324","article-title":"The role of radiotherapy in cancer treatment: Estimating optimal utilization from a review of evidence-based clinical guidelines","volume":"104","author":"Delaney","year":"2005","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13014-020-01501-x","article-title":"Recent advances in radiotherapy of breast cancer","volume":"15","author":"Haussmann","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1016\/j.jacc.2017.09.1096","article-title":"Cardiovascular Complications of Cancer Therapy","volume":"70","author":"Chang","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG), Darby, S., McGale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., and Ewertz, M. (2011). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet Lond. Engl., 378, 1707\u20131716.","DOI":"10.1016\/S0140-6736(11)61629-2"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11883-017-0658-x","article-title":"Radiation-Induced Cardiovascular Disease","volume":"19","author":"Raghunathan","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa1209825","article-title":"Risk of ischemic heart disease in women after radiotherapy for breast cancer","volume":"368","author":"Darby","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1200\/JCO.2016.69.8480","article-title":"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","volume":"35","author":"Ta","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.amjmed.2008.10.013","article-title":"The pathology of atherosclerosis: Plaque development and plaque responses to medical treatment","volume":"122","author":"Insull","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1007\/s00330-015-4143-z","article-title":"AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography","volume":"26","author":"Hetterich","year":"2016","journal-title":"Eur. Radiol."},{"key":"ref_12","first-page":"e20149","article-title":"Coronary Artery Calcium Score\u2014A Reliable Indicator of Coronary Artery Disease?","volume":"13","author":"Shreya","year":"2021","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ijrobp.2022.06.082","article-title":"Breast Cancer Radiation Therapy and the Risk of Acute Coronary Events: Insights From a Process-Oriented Model","volume":"114","author":"Simonetto","year":"2022","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.radonc.2017.10.009","article-title":"Is the coronary artery calcium score associated with acute coronary events in breast cancer patients treated with radiotherapy?","volume":"126","author":"Roos","year":"2018","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Honaryar, M.K., Allodji, R., Ferri\u00e8res, J., Panh, L., Locquet, M., Jimenez, G., Lapeyre, M., Camilleri, J., Broggio, D., and de Vathaire, F. (2022). Early Coronary Artery Calcification Progression over Two Years in Breast Cancer Patients Treated with Radiation Therapy: Association with Cardiac Exposure (BACCARAT Study). Cancers, 14.","DOI":"10.3390\/cancers14235724"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13014-021-01936-w","article-title":"Accelerated coronary calcium burden in breast cancer patients after radiotherapy: A comparison with age and race matched healthy women","volume":"16","author":"Lai","year":"2021","journal-title":"Radiat. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e007562","DOI":"10.1161\/CIRCIMAGING.117.007562","article-title":"Quantification of Coronary Atherosclerosis in the Assessment of Coronary Artery Disease","volume":"11","author":"Lee","year":"2018","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1161\/01.CIR.0000111517.69230.0F","article-title":"Detection of Calcified and Noncalcified Coronary Atherosclerotic Plaque by Contrast-Enhanced, Submillimeter Multidetector Spiral Computed Tomography","volume":"109","author":"Achenbach","year":"2004","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jcmg.2012.06.006","article-title":"Prognostic Value of Coronary CT Angiography and Calcium Score for Major Adverse Cardiac Events in Outpatients","volume":"5","author":"Hou","year":"2012","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.jacc.2012.10.054","article-title":"Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques","volume":"61","author":"Narula","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13014-016-0627-5","article-title":"Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: The BACCARAT prospective cohort study","volume":"11","author":"Jacob","year":"2016","journal-title":"Radiat. Oncol. Lond. Engl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1016\/j.ijrobp.2009.04.093","article-title":"Radiation dose-volume effects in the heart","volume":"76","author":"Gagliardi","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13014-019-1234-z","article-title":"Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: A dosimetric evaluation based on individually-determined radiation dose (BACCARAT study)","volume":"14","author":"Jacob","year":"2019","journal-title":"Radiat. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1016\/j.jcct.2009.10.011","article-title":"Measuring progression of coronary atherosclerosis with computed tomography: Searching for clarity among shades of gray","volume":"3","author":"Priester","year":"2009","journal-title":"J. Cardiovasc. Comput. Tomogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.breast.2022.07.003","article-title":"Automated coronary artery calcium scoring in patients with breast cancer to assess the risk of heart disease following adjuvant radiation therapy","volume":"65","author":"Kim","year":"2022","journal-title":"Breast Edinb. Scotl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.jacc.2006.10.079","article-title":"Long-term prognosis associated with coronary calcification: Observations from a registry of 25,253 patients","volume":"49","author":"Budoff","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jacc.2009.02.068","article-title":"Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome","volume":"54","author":"Motoyama","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C13","DOI":"10.1016\/j.jacc.2005.10.065","article-title":"Pathology of the vulnerable plaque","volume":"47","author":"Virmani","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jacc.2015.05.069","article-title":"Plaque Characterization by Coronary Computed Tomography Angiography and the Likelihood of Acute Coronary Events in Mid-Term Follow-Up","volume":"66","author":"Motoyama","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jcct.2023.02.004","article-title":"Plaque volume, composition, and fraction versus ischemia and outcomes in patients with coronary artery disease","volume":"17","author":"Kuneman","year":"2023","journal-title":"J. Cardiovasc. Comput. Tomogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1161\/01.CIR.92.3.657","article-title":"Coronary plaque disruption","volume":"92","author":"Falk","year":"1995","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e000096","DOI":"10.1136\/openhrt-2014-000096","article-title":"The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: A cohort study","volume":"1","author":"Plank","year":"2014","journal-title":"Open Heart"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s11883-019-0810-x","article-title":"Effects of Radiotherapy in Coronary Artery Disease","volume":"21","year":"2019","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/clc.22842","article-title":"The evolving view of coronary artery calcium and cardiovascular disease risk","volume":"41","author":"Thomas","year":"2018","journal-title":"Clin. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.jcmg.2017.05.010","article-title":"CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers","volume":"10","author":"Diederichsen","year":"2017","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.ijrobp.2021.03.004","article-title":"The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?","volume":"110","author":"Spoor","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1161\/CIRCULATIONAHA.121.055340","article-title":"Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population","volume":"144","author":"Persson","year":"2021","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.jcmg.2009.07.007","article-title":"Assessment of coronary plaque progression in coronary computed tomography angiography using a semiquantitative score","volume":"2","author":"Lehman","year":"2009","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e178","DOI":"10.2196\/resprot.9906","article-title":"Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer: Protocol for a European Multicenter Prospective Cohort Study (MEDIRAD EARLY HEART Study)","volume":"7","author":"Walker","year":"2018","journal-title":"JMIR Res. Protoc."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/10\/7\/299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:48Z","timestamp":1760127108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/10\/7\/299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,12]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jcdd10070299"],"URL":"https:\/\/doi.org\/10.3390\/jcdd10070299","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,12]]}}}