Diagnostic chest x-rays apparently bestow an increased risk of breast-cancer in women with mutations in BRCA susceptibility genes.
Any exposure to radiation from chest x-rays increased the women's risk by about 1.5-fold, reported Nadine Andrieu, Ph.D., and colleagues of the Institut Curie here, and other centers, in an early online release from the July 20 issue of Journal of Clinical Oncology.
Younger women who had been exposed only before the age of 20 were found to have a nearly fivefold increased risk of breast cancer associated with chest x-rays, the international team added.
"This is one of the first studies to demonstrate that women genetically predisposed to breast cancer may be more susceptible to low-dose ionizing radiation than other women," said co-author David E. Goldgar, Ph.D., who was chief of the genetic epidemiology group at the International Agency for Research on Cancer in Lyon, France, at the time the research was conducted.
"If confirmed in prospective studies, young women who are members of families known to have BRCA1 or BRCA2 mutations may wish to consider alternatives to X-ray, such as MRI," added Dr. Goldgar, who is now at the University of Utah in Salt Lake City.
In an accompanying editorial, Angela Bradbury, M.D., and Olufunmilayo I. Olopade, M.D., of the Center for Clinical Cancer Genetics at the University of Chicago, wrote that the findings suggested that breast cancer screening programs could be individualized. Women already at high risk could be screened with magnetic resonance imaging of the breast rather than conventional x-ray based mammography, they added.
"With increasing evidence supporting the high sensitivity of breast MRI for breast cancer screening in high-risk women and with ongoing research using other imaging modalities, surveillance recommendations will likely be individualized in the future," the editorialist said.
Dr. Andrieu and colleagues hypothesized that because BRCA proteins are involved in DNA repair, women with BRCA mutations that cripple DNA repair mechanisms might be more at risk from exposure to ionizing radiation than women without the mutations.
They conducted a retrospective cohort study 1,601 women with potentially harmful BRCA1 or BRCA2 mutations. The women, who were part of the International BRCA 1/2 Carrier Cohort Study, filled out questionnaires asking whether they had ever received a chest x-ray, whether they had received chest x-rays before age 20, after age 20, or during both periods, and how many x-rays they had been exposed to during each time period.
The authors found that any exposure to chest x-rays was associated with an increased risk of breast cancer, with a hazard ratio of 1.54 (P=0.007).
"In women born in 1950 or later, the relative risks of breast cancer associated with any exposure to x-ray were particularly striking (hazard ratio = 2.57; P=0.002)," the authors wrote.
"In all analyses, the estimated hazard ratio were significantly higher (all P<0.05) among women reporting more than four x-rays in at least one age period compared with women reporting no more than one to four x-rays," they added.
They also found that women who reported having x-rays only after age 20 consistently had lower hazard ratios for breast cancer than women whose first exposure was before age 20.
Among women born after 1949 who were exposed to chest x-rays only in their childhood or teens, the hazard ratio was 4.64 (95% confidence interval, 2.2 to 10.9; P <0.001) compared with women who never got chest x-rays. The increased risk may be due to exposure of still-developing breast tissue in younger women, the investigators suggested.
They did not observe any significant differences in the effect of x-ray exposure between BRCA1 and BRCA2 carriers, the authors noted.
They acknowledged that the study was limited by recall bias (women may be more likely to recall radiation to the chest if they have already been diagnosed with breast cancer) and by a lack of data on radiation dose and timing.
"Although our measures of radiation exposure are imprecise in number and timing, it is certain that the ionizing radiation dose in these women from routine chest x-rays is at least an order of magnitude lower than that found in the other radiation-exposed cohorts studied to date," they wrote.
In their editorial, Dr. Bradbury and Dr. Olopade argued that MRI surpasses mammography for sensitivity in detecting early breast cancer in asymptomatic women, and that the advantage of MRI was particularly great in diagnosis women at highest risk or with a known BRCA mutation.
- Explain to interested patients that this study applies only to women who are known to have the BRCA1 and BRCA2 mutations, which are associated with increased risk for breast cancer.
- Consider alternatives to mammography such as MRI when screening women with BRCA mutations for breast cancer.
- Be aware that in this study, the highest risk for breast cancer occurred among women with the mutations who had received ionizing radiation to the chest before the age of 20.
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