{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:50:58Z","timestamp":1775040658569,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","award":["IS-BRC-1215-20007"],"award-info":[{"award-number":["IS-BRC-1215-20007"]}],"id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA\u2013associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1\/2-associated BC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The gBRCA1\/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1\/2 Carrier Cohort Study. We used multivariable Cox proportional hazards models to investigate the association between RT (yes vs no) and CBC risk. We further stratified for BRCA status and age at PBC diagnosis (&amp;lt;40 and &amp;gt;40\u2009years). Statistical significance tests were 2-sided.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6\u2009years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P\u2009&amp;lt;\u2009.001), received chemotherapy more often (81% vs 70%, P\u2009&amp;lt;\u2009.001), and received endocrine therapy more often (50% vs 35%, P\u2009&amp;lt;\u2009.001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR]\u2009=\u20091.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR\u2009=\u20091.77; 95% CI\u2009=\u20091.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR\u2009=\u20091.29; 95% CI\u2009=\u20090.93 to 1.77; P\u2009=\u2009.39 for interaction). In the combined gBRCA1\/2 group, patients irradiated when they were younger than or older than 40 years of age at PBC diagnosis showed similar risks (HR\u2009=\u20091.38; 95% CI\u2009=\u20090.93 to 2.04 and HR\u2009=\u20091.56; 95% CI\u2009=\u20091.11 to 2.19, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>RT regimens minimizing contralateral breast dose should be considered in gBRCA1\/2 pathogenic variant carriers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djad116","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T20:54:29Z","timestamp":1687899269000},"page":"1318-1328","source":"Crossref","is-referenced-by-count":9,"title":["Contralateral breast cancer risk in patients with breast cancer and a germline-<i>BRCA1\/2<\/i> pathogenic variant undergoing radiation"],"prefix":"10.1093","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4486-4092","authenticated-orcid":false,"given":"Mark","family":"van Barele","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute , Rotterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delal","family":"Akdeniz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute , Rotterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernadette A M","family":"Heemskerk-Gerritsen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute , Rotterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Genepso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Andrieu","sequence":"additional","affiliation":[{"name":"INSERM, U900 , Paris, France"},{"name":"Institut Curie , Paris, France"},{"name":"PSL Research University , Paris, France"},{"name":"Mines ParisTech , Fontainebleau, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Nogu\u00e8s","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anticipation et de Suivi des Cancers, Oncog\u00e9n\u00e9tique Clinique, Institut Paoli-Calmettes , Marseille, France"},{"name":"Institut Paoli-Calmettes & Aix Marseille University, INSERM, IRD, SESSTIM , Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"HEBON","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christi J","family":"van Asperen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Centre , Leiden, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marijke","family":"Wevers","sequence":"additional","affiliation":[{"name":"Department for Clinical Genetics, Radboud University Medical Centre , Nijmegen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margreet G E M","family":"Ausems","sequence":"additional","affiliation":[{"name":"Division of Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Centre Utrecht , Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geertruida H","family":"de Bock","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte J","family":"Dommering","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam , Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Encarnacion B","family":"G\u00f3mez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Genetics, Maastricht University Medical Centre , Maastricht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora E","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute\u2013Antoni van Leeuwenhoek Hospital , Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thea M","family":"Mooij","sequence":"additional","affiliation":[{"name":"Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute\u2013Antoni van Leeuwenhoek Hospital , Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"EMBRACE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2444-3247","authenticated-orcid":false,"given":"Douglas F","family":"Easton","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK"},{"name":"Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge , Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonis C","family":"Antoniou","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D Gareth","family":"Evans","sequence":"additional","affiliation":[{"name":"The Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University NHS Foundation Trust , Manchester, UK"},{"name":"Genomic Medicine, Division of Evolution and Genomic Sciences, The University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust , Manchester, UK"},{"name":"Manchester Breast Centre, Oglesby Cancer Research Centre, The Christie, University of Manchester , Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Izatt","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7880-0628","authenticated-orcid":false,"given":"Marc","family":"Tischkowitz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge , Cambridge, UK"},{"name":"Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University , Montr\u00e9al, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra","family":"Frost","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Brewer","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Royal Devon & Exeter Hospital , Exeter, 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