Chest X-Rays Raise Breast Cancer Risk in Susceptible Women

http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/3632
PARIS, June 26 — 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.

Primary source: Journal of Clinical Oncology
Source reference:
Andrieu N et al. "Effect of Chest X-Rays on the Risk of Breast Cancer
Among BRCA1/2 Mutation Carriers in the International BRCA1/2 Carrier
Cohort Study." J Clin Oncol 2006. 24;21 DOI: 10.1200/JCO.2005.03.3126

Additional source: Journal of Clinical Oncology
Source reference:
Bradbury A and Olopade OI. "The Case for Individualized Screening
Recommendations for Breast Cancer." J Clin Oncol 2006. 24;21 DOI:
10.1200/JCO.2006.05.8586.