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

BMJ 2012; 345 doi: 10.1136/bmj.e5660 (Published 6 September 2012)

Cite this as: BMJ 2012;345:e5660

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Anouk Pijpe, postdoctoral research fellow1,
Nadine Andrieu, senior researcher2 3 4,
Douglas F Easton, professor5,
Ausrele Kesminiene, study coordinator6,
Elisabeth Cardis, professor7,
Catherine Noguès, oncogeneticist8,
Marion Gauthier-Villars, oncogeneticist9,
Christine Lasset, oncogeneticist10,
Jean-Pierre Fricker, oncogeneticist11,
Susan Peock, study coordinator5,
Debra Frost, research assistant5,
D Gareth Evans, professor12,
Rosalind A Eeles, clinical cancer geneticist13,
Joan Paterson, clinical geneticist14,
Peggy Manders, postdoctoral research fellow1 15,
Christi J van Asperen, clinical geneticist16,
Margreet G E M Ausems, clinical geneticist17,
Hanne Meijers-Heijboer, clinical geneticist18,
Isabelle Thierry-Chef, researcher6,
Michael Hauptmann, statistician1,
David Goldgar, senior researcher19,
Matti A Rookus, senior research fellow1,
Flora E van Leeuwen, professor1
on behalf of GENEPSO, EMBRACE, and HEBON

Author Affiliations

Correspondence to: F E van Leeuwen f.v.leeuwen@nki.nl

Accepted 10 August 2012

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=".0020" 0.85="0.85" 1.43="1.43" 1.63="1.63" 1.75="1.75" 1.78="1.78" 2.40="2.40" 2.77="2.77" 20="20" 3.58="3.58" 3.84="3.84" 30="30" 4.25="4.25" 8.79="8.79" a="a" age="age" also="also" an="an" analyses="analyses" analysis="analysis" and="and" associated="associated" before="before" breast="breast" by="by" cancer="cancer" caused="caused" compared="compared" confounding="confounding" diagnostic="diagnostic" different="different" exposure.="exposure." family="family" finding="finding" gy="gy" hazard="hazard" history.="history." history="history" increased="increased" increasing="increasing" indication="indication" mammography="mammography" no="no" not="not" number="number" of="of" on="on" p="p" pattern="pattern" procedures="procedures" radiographs="radiographs" ratio="ratio" respectively.="respectively." risk="risk" sensitivity="sensitivity" showed="showed" that="that" the="the" this="this" to="to" types="types" was="was" were="were" with="with">

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.