Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2013 Sep;49(14):2979-85.
doi: 10.1016/j.ejca.2013.04.028. Epub 2013 May 21.

Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: a WECARE study report

Jonine L Bernstein  1 , Duncan C Thomas, Roy E Shore, Mark Robson, John D Boice Jr, Marilyn Stovall, Michael Andersson, Leslie Bernstein, Kathleen E Malone, Anne S Reiner, Charles F Lynch, Marinela Capanu, Susan A Smith, Lina Tellhed, Sharon N Teraoka, Colin B Begg, Jorgen H Olsen, Lene Mellemkjaer, Xiaolin Liang, Anh T Diep, Ake Borg, Patrick Concannon, Robert W Haile; WECARE Study Collaborative Group
Collaborators, Affiliations
Multicenter Study

Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: a WECARE study report

Jonine L Bernstein et al. Eur J Cancer. 2013 Sep.

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].

Keywords: BRCA1/BRCA2; Contralateral breast cancer; Radiotherapy.

PubMed Disclaimer

References

    1. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. 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. 2011;378(9804):1707–16. - PMC - PubMed
    1. Preston DL, Mattsson A, Holmberg E, Shore R, Hildreth NG, Boice JD., Jr Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiat Res. 2002;158(2):220–35. - PubMed
    1. Ronckers CM, Erdmann CA, Land CE. Radiation and breast cancer: a review of current evidence. Breast Cancer Res. 2005;7(1):21–32. - PMC - PubMed
    1. Bhatti P, Struewing JP, Alexander BH, Hauptmann M, Bowen L, Mateus-Pereira LH, et al. Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. Radiologic technologists. Int J Cancer. 2008;122(1):177–82. - PubMed
    1. Turnbull C, Mirugaesu N, Eeles R. Radiotherapy and genetic predisposition to breast cancer. Clin Oncol (R Coll Radiol) 2006;18(3):257–67. - PubMed

Publication types