New biological insights on the link between radiation exposure and breast cancer risk.

ABSTRACT

Radiation exposure is a well-documented risk factor for breast cancer in women. Compelling epidemiological evidence in different exposed populations around the world demonstrate that excess breast cancer increases with radiation doses above 10 cGy. Both frequency and type of breast cancer are affected by prior radiation exposure. Many epidemiological studies suggest that radiation risk is inversely related to age at exposure; exposure during puberty poses the greatest risk while exposures past the menopause appear to carry very low risk. These observations are supported by experimental studies in mice and rats, which together provide the basis for the pubertal 'window of susceptibility' hypothesis for carcinogenic exposure. One line of experimental investigation suggests that the pubertal epithelium is more sensitive because DNA damage responses are less efficient, an other suggests that radiation affects stem cells self-renewal. A recent line of investigation suggests that the irradiated microenvironment mediates cancer risk. Studying the biological basis for radiation effects provides potential routes for protection in vulnerable populations, which include survivors of childhood cancers, as well as insights into the biology for certain types of sporadic cancer.