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Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation
M. van Barele, D. Akdeniz, BAM. Heemskerk-Gerritsen, Genepso, N. Andrieu, C. Noguès, HEBON, CJ. van Asperen, M. Wevers, MGEM. Ausems, GH. de Bock, CJ. Dommering, EB. Gómez-García, FE. van Leeuwen, TM. Mooij, EMBRACE, DF. Easton, AC. Antoniou, DG....
Language English Country United States
Document type Journal Article
Grant support
IS-BRC-1215-20007
NIHR
NLK
Free Medical Journals
from 1996 to 1 year ago
Open Access Digital Library
from 1996-01-01
PubMed
37369040
DOI
10.1093/jnci/djad116
Knihovny.cz E-resources
- MeSH
- Cohort Studies MeSH
- Humans MeSH
- Breast Neoplasms * genetics radiotherapy drug therapy MeSH
- Prospective Studies MeSH
- BRCA1 Protein genetics MeSH
- BRCA2 Protein genetics MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: 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-associated 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. METHODS: 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 (<40 and >40 years). Statistical significance tests were 2-sided. RESULTS: Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6 years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P < .001), received chemotherapy more often (81% vs 70%, P < .001), and received endocrine therapy more often (50% vs 35%, P < .001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR] = 1.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR = 1.77; 95% CI = 1.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR = 1.29; 95% CI = 0.93 to 1.77; P = .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 = 1.38; 95% CI = 0.93 to 2.04 and HR = 1.56; 95% CI = 1.11 to 2.19, respectively). CONCLUSIONS: RT regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.
Centre for Cancer Genetic Epidemiology Department of Oncology University of Cambridge Cambridge UK
Centre for Personalized Response Monitoring in Oncology Odense University Hospital Odense Denmark
Department for Clinical Genetics Radboud University Medical Centre Nijmegen the Netherlands
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Genetics Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam the Netherlands
Department of Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK
Department of Clinical Genetics Leiden University Medical Centre Leiden the Netherlands
Department of Clinical Genetics Odense University Hospital Odense Denmark
Department of Clinical Genetics Royal Devon and Exeter Hospital Exeter UK
Department of Clinical Research University of Southern Denmark Odense Denmark
Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland
Department of Genetics Maastricht University Medical Centre Maastricht the Netherlands
Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam the Netherlands
Department of Molecular Genetics National Institute of Oncology Budapest Hungary
Institut Paoli Calmettes and Aix Marseille University INSERM IRD SESSTIM Marseille France
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Mines ParisTech Fontainebleau France
References provided by Crossref.org
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- $a Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation / $c M. van Barele, D. Akdeniz, BAM. Heemskerk-Gerritsen, Genepso, N. Andrieu, C. Noguès, HEBON, CJ. van Asperen, M. Wevers, MGEM. Ausems, GH. de Bock, CJ. Dommering, EB. Gómez-García, FE. van Leeuwen, TM. Mooij, EMBRACE, DF. Easton, AC. Antoniou, DG. Evans, L. Izatt, M. Tischkowitz, D. Frost, C. Brewer, E. Olah, J. Simard, CF. Singer, M. Thomassen, K. Kast, K. Rhiem, C. Engel, M. de la Hoya, L. Foretová, A. Jakubowska, A. Jager, MGA. Sattler, MK. Schmidt, MJ. Hooning
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- $a BACKGROUND: 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-associated 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. METHODS: 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 (<40 and >40 years). Statistical significance tests were 2-sided. RESULTS: Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6 years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P < .001), received chemotherapy more often (81% vs 70%, P < .001), and received endocrine therapy more often (50% vs 35%, P < .001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR] = 1.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR = 1.77; 95% CI = 1.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR = 1.29; 95% CI = 0.93 to 1.77; P = .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 = 1.38; 95% CI = 0.93 to 2.04 and HR = 1.56; 95% CI = 1.11 to 2.19, respectively). CONCLUSIONS: RT regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.
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