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

Author:
  • Jonine L. Bernstein
  • Duncan C. Thomas
  • Roy E. Shore
  • Mark Robson
  • John D. Jr. Boice
  • 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
  • Åke Borg
  • Patrick Concannon
  • Robert W. Haile
Publishing year: 2013
Language: English
Pages: 2979-2985
Publication/Series: European Journal of Cancer
Volume: 49
Issue: 14
Document type: Journal article
Publisher: Elsevier

Abstract english

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.

Keywords

  • Cancer and Oncology
  • Contralateral breast cancer
  • Radiotherapy
  • BRCA1/BRCA2

Other

Published
  • ISSN: 1879-0852
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90