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

Jonine L Bernstein; Duncan C Thomas; Roy E Shore; Mark Robson; John D 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; Ake Borg; Patrick Concannon; Robert W Haile; The WECARE Study Collaborative Group

doi:10.1016/j.ejca.2013.04.028

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

Journal article

Peer reviewed

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

Jonine L Bernstein, Duncan C Thomas, Roy E Shore, Mark Robson, John D Boice, Marilyn Stovall, Michael Andersson, Leslie Bernstein, Kathleen E Malone, Anne S Reiner, …

European journal of cancer (1990), Vol.49(14), pp.2979-2985

09/2013

DOI: 10.1016/j.ejca.2013.04.028

PMCID: PMC3755053

PMID: 23706288

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Abstract

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. 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. Among women treated with radiation, the mean radiation dose was 1.1Gy (range=0.02–6.2Gy). 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. 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. All work associated with this study was supported by the U.S. National Cancer Institute [R01CA097397, U01CA083178].

Radiotherapy

Contralateral breast cancer

BRCA1/BRCA2

Details

Title: Subtitle: Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report
Creators: Jonine L Bernstein - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Duncan C Thomas - Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
Roy E Shore - Department of Environmental Medicine, New York University, New York, NY, USA
Mark Robson - Department of Clinical Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
John D Boice - Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
Marilyn Stovall - Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Michael Andersson - Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Leslie Bernstein - Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA
Kathleen E Malone - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Anne S Reiner - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Charles F Lynch - Department of Epidemiology, University of Iowa, Iowa City, IA, USA
Marinela Capanu - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Susan A Smith - Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Lina Tellhed - Department of Oncology, Clinical Sciences, Lund University, Sweden
Sharon N Teraoka - Department of Biochemistry and Molecular Genetics and Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
Colin B Begg - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Jorgen H Olsen - Danish Cancer Society Research Center, Copenhagen, Denmark
Lene Mellemkjaer - Danish Cancer Society Research Center, Copenhagen, Denmark
Xiaolin Liang - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Anh T Diep - Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
Ake Borg - Department of Oncology, Clinical Sciences, Lund University, Sweden
Patrick Concannon - Department of Biochemistry and Molecular Genetics and Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
Robert W Haile - Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
The WECARE Study Collaborative Group
Resource Type: Journal article
Publication Details: European journal of cancer (1990), Vol.49(14), pp.2979-2985
DOI: 10.1016/j.ejca.2013.04.028
PMID: 23706288
PMCID: PMC3755053
NLM abbreviation: Eur J Cancer
ISSN: 0959-8049
eISSN: 1879-0852
Publisher: Elsevier Ltd
Language: English
Date published: 09/2013
Academic Unit: Epidemiology
Record Identifier: 9983995149102771

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