Analysis of breast cancer in the Massachusetts TB fluoroscopy cohort and in the Japanese A-bomb survivors, taking account of dosimetric error and curvature in the A-bomb dose response: absence of evidence of reduction of risk following fractionated irrad

Abstract

Breast cancer has occurred in excess among women exposed briefly to atomic bomb radiation and among those exposed repeatedly over many years to medical radiation for tuberculosis (TB). The breast cancer excess is strongly dependent on age at exposure, with risk highest among the young and small or non-existent when exposure occurs past the menopausal ages. The linear excess relative risk coefficient of breast cancer incidence in the Japanese A-bomb survivor data, however, is significantly higher (two-sided P = 0.04) than that in the Massachusetts TB fluoroscopy data; this remains the case (two-sided P = 0.03) if account is also taken of possible curvature in the A-bomb survivor dose response and random dosimetric errors. The best estimate of the ratio between the linear excess relative risk coefficients for the Japanese and Massachusetts cohorts is 2.11 (95% CI 1.05, 4.95), or 3.18 (95% CI 1.19, 8.21) if account is taken of dosimetric error and possible curvature in the A-bomb survivor data. However, this higher relative excess risk is attributable to the lower baseline risk of breast cancer among Japanese compared with the Massachusetts women, and the linear excess absolute breast cancer risk coefficients in the two data sets are statistically indistinguishable (two-sided P = 0.32). The best estimate of the ratio between the excess absolute risk coefficients among Japanese and Massachusetts women is 0.73 (95% CI 0.41, 1.44). Again, if account is also taken of possible curvature in the A-bomb survivor dose response and random dosimetric errors, these results are not substantially altered; in this case the best estimate of the ratio between the linear excess absolute risk coefficients among Japanese and Massachusetts women is 1.07 (95% CI 0.42, 2.38) (two-sided P = 0.86). These results are not sensitive to the assumed neutron relative biological effectiveness for the Japanese data, or analyses over restricted dose ranges in this data set. In general, there are no marked differences between the Massachusetts and Japanese data sets in the age and time distribution of risk of radiation-induced breast cancer. These data provide little evidence for a reduction in breast cancer risk following fractionated irradiation.