Radiation and breast carcinogenesis

With the possible exception of radiation-induced leukemia, more is known about radiation-induced breast cancer than any other malignancy. Fourteen cohort studies have provided quantitative information on the level of risk following a wide range of doses in different populations around the world. Comprehensive studies have been conducted in Canada, Germany, Japan, Sweden and other Nordic countries, the United Kingdom, and the USA [Table I in text]. Key features are the linearity in the dose response (i.e., a straight line adequately fits the observed data), and the effect modification of age at exposure (i.e., risk is inversely related to exposure age and exposures past the menopausal ages appear to carry a very low risk); and the minimal effect of fractionating dose on subsequent risk. A recent combined analysis of almost 78,000 women and 1,500 breast cancer cases from eight cohorts confirmed the downturn in risk at the highest dose levels (related in part to the killing of cells rather than transformation) and that fractionation of dose has little influence on risk, at least on an absolute scale. It is not known whether persons predisposed to cancer are at enhanced risk of radiation-induced breast cancer from low-dose exposures, although this seems unlikely. New data on the effects of high doses following childhood exposures will be forthcoming from long-term studies of the survivors of childhood cancer.