Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study

Background: Screening mammography is associated with a small dose of radiation to the breast, and women with increased genetic risk might be particularly sensitive to the DNA-damaging effects of ionising radiation. We aimed to assess whether exposure to ionising radiation through mammography screening was associated with risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Methods: We identified 1600 cases of breast cancer and 1600 controls without breast cancer who were matched for BRCA mutation, date of birth (within 1 year), and country of residence from an international registry of BRCA1 and BRCA2 mutation carriers. We used a questionnaire to inquire about whether participants had ever had screening mammography, and, if so, the age at which they first had the procedure. Results: We found no association between ever having screening mammography and risk of breast cancer (odds ratio [OR] 1·03 [95% CI 0·85-1·25], adjusted for parity, oral-contraceptive use, ethnic origin, and bilateral oophorectomy). The association was much the same for BRCA1 mutation carriers and BRCA2 mutation carriers (1·04 [0·84-1·29] vs 1·06 [0·67-1·66], respectively, adjusted for parity, oral-contraceptive use, ethnic origin, and bilateral oophorectomy). Interpretation: These findings do not lend support to the idea that exposure to ionising radiation through routine screening mammography contributes substantially to the burden of breast cancer in BRCA1 and BRCA2 mutation carriers. Prospective studies are needed to confirm the results of this initial report, and, where possible, these studies should assess a more appropriate endpoint of total exposure.