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

Bernstein, Jonine L.; Thomas, Duncan C.; Shore, Roy E.; Robson, Mark; Boice, John D. Jr.; Stovall, Marilyn; Andersson, Michael; Bernstein, Leslie; Malone, Kathleen E. and Reiner, Anne S., et al. (2013) In European Journal of Cancer 49(14). p.2979-2985
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... (More)
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]. (C) 2013 Elsevier Ltd. All rights reserved. (Less)
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keywords
Contralateral breast cancer, Radiotherapy, BRCA1/BRCA2
in
European Journal of Cancer
volume
49
issue
14
pages
2979 - 2985
publisher
IFAC & Elsevier Ltd.
external identifiers
  • wos:000323604700004
  • scopus:84883052621
ISSN
1879-0852
DOI
10.1016/j.ejca.2013.04.028
language
English
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yes
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8262a611-bd0d-4e60-80f1-67293a607a58 (old id 4062769)
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2014-03-03 08:12:10
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@article{8262a611-bd0d-4e60-80f1-67293a607a58,
  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]. (C) 2013 Elsevier Ltd. All rights reserved.},
  author       = {Bernstein, Jonine L. and Thomas, Duncan C. and Shore, Roy E. and Robson, Mark and Boice, John D. Jr. and Stovall, Marilyn and Andersson, Michael and Bernstein, Leslie and Malone, Kathleen E. and Reiner, Anne S. and Lynch, Charles F. and Capanu, Marinela and Smith, Susan A. and Tellhed, Lina and Teraoka, Sharon N. and Begg, Colin B. and Olsen, Jorgen H. and Mellemkjaer, Lene and Liang, Xiaolin and Diep, Anh T. and Borg, Åke and Concannon, Patrick and Haile, Robert W.},
  issn         = {1879-0852},
  keyword      = {Contralateral breast cancer,Radiotherapy,BRCA1/BRCA2},
  language     = {eng},
  number       = {14},
  pages        = {2979--2985},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report},
  url          = {http://dx.doi.org/10.1016/j.ejca.2013.04.028},
  volume       = {49},
  year         = {2013},
}