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. 2012 Sep 6:345:e5660.
doi: 10.1136/bmj.e5660.

Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK)

Anouk Pijpe  1 , Nadine Andrieu, Douglas F Easton, Ausrele Kesminiene, Elisabeth Cardis, Catherine Noguès, Marion Gauthier-Villars, Christine Lasset, Jean-Pierre Fricker, Susan Peock, Debra Frost, D Gareth Evans, Rosalind A Eeles, Joan Paterson, Peggy Manders, Christi J van Asperen, Margreet G E M Ausems, Hanne Meijers-Heijboer, Isabelle Thierry-Chef, Michael Hauptmann, David Goldgar, Matti A Rookus, Flora E van Leeuwen; GENEPSO; EMBRACE; HEBON
Collaborators, Affiliations

Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK)

Anouk Pijpe et al. BMJ. .

Abstract

Objective: To estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations.

Design: Retrospective cohort study (GENE-RAD-RISK).

Setting: Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands,

Participants: 1993 female carriers of BRCA1/2 mutations recruited in 2006-09.

Main outcome measure: Risk of breast cancer estimated with a weighted Cox proportional hazards model with a time dependent individually estimated cumulative breast dose, based on nominal estimates of organ dose and frequency of self reported diagnostic procedures. To correct for potential survival bias, the analysis excluded carriers who were diagnosed more than five years before completion of the study questionnaire.

Results: In carriers of BRCA1/2 mutations any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of breast cancer (hazard ratio 1.90, 95% confidence interval 1.20 to 3.00), with a dose-response pattern. The risks by quarter of estimated cumulative dose <0.0020 Gy, ≥ 0.0020-0.0065 Gy, ≥ 0.0066-0.0173 Gy, and ≥ 0.0174 Gy were 1.63 (0.96 to 2.77), 1.78 (0.88 to 3.58), 1.75 (0.72 to 4.25), and 3.84 (1.67 to 8.79), respectively. Analyses on the different types of diagnostic procedures showed a pattern of increasing risk with increasing number of radiographs before age 20 and before age 30 compared with no exposure. A history of mammography before age 30 was also associated with an increased risk of breast cancer (hazard ratio 1.43, 0.85 to 2.40). Sensitivity analysis showed that this finding was not caused by confounding by indication of family history.

Conclusion: In this large European study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation before age 30 was associated with an increased risk of breast cancer at dose levels considerably lower than those at which increases have been found in other cohorts exposed to radiation. The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: DFE is board member of Genome Canada. RAE receives royalties for the book Genetic Predisposition to Cancer, has received educational grants from Tepnel, Illumina, and Vista Diagnostics and has received honoraria for BRCA-related lectures from MD Anderson and University of Southampton. DG receives royalties from BRCA1 testing.

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