Mammography—oncogenecity at low doses

Abstract

Controversy exists regarding the biological effectiveness of low energyx-rays used for mammography breast screening. Recent radiobiology studieshave provided compelling evidence that these low energy x-rays may be4.42 ± 2.02 times more effective in causing mutational damage than higher energy x-rays.These data include a study involving in vitro irradiation of a human cell line using amammography x-ray source and a high energy source which matches the spectrum ofradiation observed in survivors from the Hiroshima atomic bomb. Current radiation riskestimates rely heavily on data from the atomic bomb survivors, and a direct comparisonbetween the diagnostic energies used in the UK breast screening programme and those usedfor risk estimates can now be made. Evidence highlighting the increase in relative biologicaleffectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that therisks of radiation-induced breast cancers for mammography x-rays are potentiallyunderestimated by a factor of four. A pooled analysis of three measurementsgives a maximal RBE (for malignant transformation of human cells in vitro) of4.02 ± 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higherenergy x-rays.For the majority of women in the UK NHS breast screening programme, it is shown thatthe benefit safely exceeds the risk of possible cancer induction even when this higherbiological effectiveness factor is applied. The risk/benefit analysis, however, implies theneed for caution for women screened under the age of 50, and particularly for those with afamily history (and therefore a likely genetic susceptibility) of breast cancer.In vitro radiobiological data are generally acquired at high doses, and there are differentextrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro datahave indicated a potential suppressive effect at very low dose rates and doses. Whilstmammography is a low dose exposure, it is not a low dose rate examination, andprotraction of dose should not be confused with fractionation. Although there is potentialfor a suppressive effect at low doses, recent epidemiological data, and several internationalradiation risk assessments, continue to promote the linear no-threshold (LNT) model.Finally, recent studies have shown that magnetic resonance imaging (MRI) is moresensitive than mammography in detecting invasive breast cancer in women with a geneticsensitivity. Since an increase in the risk associated with mammographic screening wouldblur the justification of exposure for this high risk subgroup, the use of other (non-ionising)screening modalities is preferable.