Clin Genet 2011: 79: 431 – 437 Printed in Singapore. All rights reserved  2011 John Wiley & Sons A/S CLINICAL GENETICS doi: 10.1111/j.1399-0004.2010.01604.x Original Article Breast cancer after bilateral risk-reducing mastectomy Skytte A-B, Cr¨ uger D, Gerster M, Lænkholm A-V, Lang C, Brøndum-Nielsen K, Andersen MK, Sunde L, Kølvraa S, Gerdes A-M. Breast cancer after bilateral risk-reducing mastectomy. Clin Genet 2011: 79: 431–437.  John Wiley & Sons A/S, 2011 This study aims to evaluate the incidence of breast cancer after risk-reducing mastectomy (RRM) in healthy BRCA mutation carriers. This study is a long-term follow-up of 307 BRCA mutation carriers of whom 96 chose RRM. None of the study participants had a previous history of breast or ovarian cancer nor had they undergone RRM or risk-reducing bilateral salpingo-oophorectomy (BSO) prior to the time of BRCA testing. The annual incidence of post-mastectomy breast cancer was 0.8% compared with 1.7% in the non-operated group. Implications of these findings in relation to genetic counseling and future management are discussed. Conflict of interest None to declare. A-B Skytte a,b , D Cr ¨ uger a , M Gerster c , A-V Lænkholm d , C Lang e , K Brøndum-Nielsen f,g , MK Andersen h , L Sunde i , S Kølvraa a,b and A-M Gerdes g,h,j a Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark, b Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark, c Department of Biostatistics, Institute of Public Health, University of Southern Denmark, Odense, Denmark, d Department of Pathology, Rigshospitalet, Copenhagen, Denmark, e Department of Breast Surgery, Herlev Hospital, Copenhagen, Denmark, f Department of Clinical Genetics, the Kennedy Center, Copenhagen, Denmark, g Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark, h Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark, i Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark, and j Department of Clinical Genetics, Odense University Hospital, Odense, Denmark Key words: BRCA1 – BRCA2 – breast cancer – mastectomy – risk – risk reduction Corresponding author: Anne-Bine Skytte, Department of Genetics, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Tel.: +45 79406556; fax: +45 79406871; e-mail: Anne-Bine.Skytte@ slb.regionsyddanmark.dk Received 9 September 2010, revised and accepted for publication 30 November 2010 Women with a germline mutation in the BRCA1 or BRCA2 gene are facing a high lifetime risk of developing breast and/or ovarian cancer. Their average lifetime breast cancer risk is estimated to be 46–90% (1–6). The size of the risk and their age at onset depend on the gene and the mutation involved. Thus, BRCA1 carriers develop cancer more often and at a younger age than BRCA2 car- riers (3). To counter the risk of developing breast cancer, the BRCA carriers may choose between 431