• Anouk Pijpe, 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, and HEBON.
• Netherlands Cancer Institute, Department of Epidemiology and Biostatistics, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
• BMJ. 2012 Jan 1;345:e5660.

ObjectiveTo estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations.DesignRetrospective cohort study (GENE-RAD-RISK).SettingThree nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands,Participants1993 female carriers of BRCA1/2 mutations recruited in 2006-09.Main Outcome MeasureRisk 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.ResultsIn 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.ConclusionIn 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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