RADIATION-INDUCED BREAST-CANCER - LONG-TERM FOLLOW-UP OF RADIATION-THERAPY FOR BENIGN BREAST DISEASE

Background. From the 1920s through the 1950s, radiation therapy was used in Sweden as a treatment for benign breast diseases. It is now known that exposure of the breast to ionizing radiation increases the relative risk of subsequent breast cancer, especially for younger women. However, the degree to which the patient' s age contributes to the elevation of risk for subsequent development of breast cancer is not yet completely understood. Purpose: The purpose was to study the risk of breast cancer after irradiation of the female breast and, in particular, to analyze the duration of the effect and the risk for women older than 40 years at first exposure. Methods: In this cohort study, data were obtained through population-based registers. The exposed group consisted of 1216 women (median age, 40 years) who, during the period spanning 1925 through 1954, received radiation therapy for benign breast disease. The reference group consisted of 1874 women (median age, 36 years) who had the same diagnosis during that time period but did not receive radiation therapy. The radiation doses were determined from the original medical records (mean dose, 5.8 Gy; range, 0.003-50.1 Gy). The follow-up lasted up to 60 years after first exposure. The incidence rate ratio was analyzed with Poisson regression models. Results: The total number of breast cancers in the exposed cohort was 198 versus 101 in the unexposed cohort. Overall, the radiation-associated incidence rate ratio was 3.58 (95% confidence interval = 2.77-4.63). The dose-response gradient was statistically significant (P<.001) but leveled off at higher doses. The incidence rate ratios decreased starting about 25 years after first exposure but were at increased levels throughout the entire follow-up period. The incidence rate ratio decreased with age at first exposure but was significantly increased (P<.001) even when the age at time of first exposure was greater than 40 years. Conclusions: Total dose, age at first exposure, and time since first exposure were all determinants of the incidence rate ratio of breast cancer after exposure of the breast to ionizing radiation. A statistically significant increase in the incidence of breast cancer following radiation treatment of various benign breast diseases was observed even among women older than 40 years at the time of first treatment. Implications: These findings need to be considered when weighing the relative benefits versus risks of generalized screening of younger women for breast cancer by mammography.