Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report Journal Article


Authors: Bernstein, J. L.; Thomas, D. C.; Shore, R. E.; Robson, M.; Boice, J. D. Jr; Stovall, M.; Andersson, M.; Bernstein, L.; Malone, K. E.; Reiner, A. S.; Lynch, C. F.; Capanu, M.; Smith, S. A.; Tellhed, L.; Teraoka, S. N.; Begg, C. B.; Olsen, J. H.; Mellemkjaer, L.; Liang, X.; Diep, A. T.; Borg, A.; Concannon, P.; Haile, R. W.
Article Title: Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report
Abstract: Background Women with germline BRCA1 or BRCA2 (BRCA1/BRCA2) mutations are at very high risk of developing breast cancer, including asynchronous contralateral breast cancer (CBC). BRCA1/BRCA2 genes help maintain genome stability and assist in DNA repair. We examined whether the risk of CBC associated with radiation treatment was higher among women with germline BRCA1/BRCA2 mutations than among non-carriers. Methods A population-based, nested case-control study was conducted within a cohort of 52,536 survivors of unilateral breast cancer (UBC). Cases were 603 women with CBC and controls were 1199 women with UBC individually matched on age at diagnosis, race, year of first diagnosis and cancer registry. All women were tested for BRCA1 and BRCA2 mutations. Radiation absorbed dose from the initial radiotherapy (RT) to the CBC location within the contralateral breast was reconstructed from measurements in a tissue-equivalent phantom and details available in the therapy records. Findings Among women treated with radiation, the mean radiation dose was 1.1 Gy (range = 0.02-6.2 Gy). Risk of developing CBC was elevated among women who carried a deleterious BRCA1/BRCA2 mutation (rate ratio, RR = 4.5, confidence interval, CI = 3.0-6.8), and also among those treated with RT (RR = 1.2, CI = 1.0-1.6). However, among mutation carriers, an incremental increase in risk associated with radiation dose was not statistically significant. Interpretation Multiplicative interaction of RT with mutation status would be reflected by a larger association of RT with CBC among carriers than among non-carriers, but this was not apparent. Accordingly, there was no clear indication that carriers of deleterious BRCA/BRCA2 mutations were more susceptible to the carcinogenic effects of radiation than non-carriers. These findings are reassuring and have important clinical implications for treatment decisions and the clinical management of patients harbouring deleterious BRCA1/BRCA2 mutations. Funding All work associated with this study was supported by the U.S. National Cancer Institute [R01CA097397, U01CA083178]. © 2013 Elsevier Ltd. All rights reserved.
Keywords: adult; controlled study; middle aged; gene mutation; major clinical study; case-control studies; cancer radiotherapy; radiation dose; dna repair; genetic predisposition to disease; cohort studies; breast cancer; breast; logistic models; radiotherapy; risk factors; breast neoplasms; brca1 protein; brca2 protein; heterozygote; cancer survivor; radiation dosage; genomic instability; multivariate analysis; population based case control study; contralateral breast cancer; brca1/brca2
Journal Title: European Journal of Cancer
Volume: 49
Issue: 14
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2013-09-01
Start Page: 2979
End Page: 2985
Language: English
DOI: 10.1016/j.ejca.2013.04.028
PROVIDER: scopus
PMCID: PMC3755053
PUBMED: 23706288
DOI/URL:
Notes: --- - "Export Date: 25 September 2013" - "CODEN: EJCAE" - "Source: Scopus"
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MSK Authors
  1. Anne S Reiner
    122 Reiner
  2. Colin B Begg
    239 Begg
  3. Mark E Robson
    368 Robson
  4. Marinela Capanu
    211 Capanu
  5. Jonine L Bernstein
    104 Bernstein
  6. Xiaolin Liang
    41 Liang