Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study

• Published in: Breast cancer research : BCR Vol. 9; no. 2; p. R26
• Main Authors: Broeks, Annegien, Braaf, Linde M, Huseinovic, Angelina, Nooijen, Anke, Urbanus, Jos, Hogervorst, Frans B L, Schmidt, Marjanka K, Klijn, Jan G M, Russell, Nicola S, Van Leeuwen, Flora E, Van 't Veer, Laura J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.01.2007; National Library of Medicine - MEDLINE Abstracts; BioMed Central
• Subjects: Adult; Analysis; Ataxia Telangiectasia Mutated Proteins; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Case studies; Cell Cycle Proteins - genetics; Checkpoint Kinase 2; DNA Damage; DNA Repair; DNA-Binding Proteins - genetics; Female; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Middle Aged; Neoplasms, Radiation-Induced - diagnosis; Neoplasms, Radiation-Induced - genetics; Protein Serine-Threonine Kinases - genetics; Risk Factors; Tumor Suppressor Proteins - genetics
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/bcr1668

Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer. We evaluated the contribution of germline mutations in the DDRP genes BRCA1, BRCA2, CHEK2 and ATM to the risk of radiation-induced contralateral breast cancer (CBC). The germline mutation frequency was assessed, in a case-only study, in women who developed a CBC after they had a first breast cancer diagnosed before the age of 50 years, and who were (n = 169) or were not (n = 78) treated with radiotherapy for their first breast tumour. We identified 27 BRCA1, 5 BRCA2, 15 CHEK2 and 4 truncating ATM germline mutation carriers among all CBC patients tested (21%). The mutation frequency was 24.3% among CBC patients with a history of radiotherapy, and 12.8% among patients not irradiated for the first breast tumour (odds ratio 2.18 (95% confidence interval 1.03 to 4.62); p = 0.043). The association between DDRP germline mutation carriers and risk of radiation-induced CBC seemed to be strongest in women who developed their second primary breast tumour at least 5 years after radiotherapy. Those patients had an odds ratio of 2.51 (95% confidence interval 1.03 to 6.10; p = 0.049) of developing radiation-induced breast cancer, in comparison with non-carriers. This study shows that carriers of germline mutations in a DDRP gene have an increased risk of developing (contralateral) breast cancer after radiotherapy; that is, over and above the risk associated with their carrier status. The increased risk indicates that knowledge of germline status of these DDRP genes at the time of breast cancer diagnosis may have important implications for the choice of treatment.