Diagnostic Radiation Exposure May Raise Breast Cancer Risk in Some BRCA1/2 Mutation CarriersRadiation from conventional x-rays, mammograms, and other diagnostic tests before age 30 may increase the risk of breast cancer in women who carry BRCA1 or BRCA2 gene mutations. In a large, retrospective cohort study, this increased risk was seen at radiation doses considerably lower than those associated with increased risk of breast cancer in other cohorts exposed to radiation.
The findings, from an analysis of women in France, the Netherlands, and the United Kingdom who participated in the GENE-RAD-RISK study, were reported September 6 in the British Medical Journal.
Exposure to ionizing radiation is an established risk factor for breast cancer, particularly when the exposure occurs at an early age. Because the BRCA1 and BRCA2 proteins are important in repairing DNA damage, including damage caused by radiation, researchers have hypothesized that carriers of a mutation in one of these genes might be more sensitive than the general population to ionizing radiation. But previous studies designed to answer this question have yielded inconsistent results.
The new study, led by Dr. Flora van Leeuwen of the Netherlands Cancer Institute in Amsterdam, focused on 1,122 women aged 18 or older who were known to carry a BRCA1 or BRCA2 mutation. The women reported their histories of all diagnostic procedures involving radiation to the chest or shoulders. Researchers used this information to estimate the cumulative dose of radiation to the breast for each woman. They then used national registries or medical records to confirm breast cancer diagnoses among the participants.
When compared with no exposure, any exposure to diagnostic radiation before age 30 was associated with almost double the risk of breast cancer in BRCA1/2 mutation carriers. Women who received the highest doses of radiation before age 30 had an almost fourfold higher risk. By contrast, there was no evidence of an increased breast cancer risk associated with exposure at ages 30 to 39.
Because women with BRCA1 or BRCA2 mutations have a greatly increased risk of developing breast cancer, some guidelines recommend annual mammograms beginning at age 25 to 35 for these women.
These findings “support the recommendation to use non-ionising radiation imaging techniques (such as MRI) as the main tool for surveillance in young BRCA1 and BRCA2 mutation carriers,” the authors concluded.
Dr. Barry Kramer, director of NCI’s Division of Cancer Prevention, noted that the study “helps refine our knowledge” about the connection between radiation exposure and breast cancer risk in people who may be particularly sensitive to the effects of ionizing radiation. However, he cautioned, “the evidence in this study is not definitive.”
The authors acknowledge that their reliance on self report of prior radiation exposure could introduce statistical bias. “People who have cancer may be more likely than those without cancer to recall any radiation that they had,” Dr. Kramer explained.
Until more definitive evidence is available, he continued, “Women who carry BRCA1 or BRCA2 mutations ought to know what we do and don’t know.” Physicians should review the screening and prevention options with each woman and help her consider the potential benefits and downsides of each, he concluded.
Further reading: “Clinical Management of BRCA Mutation Carriers”