The Risk of Secondary Malignancies Over 30 Years After the Treatment of Non-Hodgkin Lymphoma T ward et al. 1 reported a significantly elevated risk of mesothe- lioma in a population-based study of survivors of non-Hodgkin lymphoma who were treated with radiation. Although the authors were not aware of other population-based studies that describe an increased risk of mesothelioma after irradiation, we reported a significantly elevated relative risk (RR) of mesothelioma among irradiated testicular cancer patients (RR, 4.0; 95% confidence interval [95% CI], 2.0-8.1; 14 cases). 2 Herein, we provide to our knowledge the first description of significant excesses of mesothelioma (40 cases) among 376,825 breast cancer patients who had survived for 1 year and were reported to population-based cancer registries in Sweden, Denmark, Finland, and Norway between January 1, 1943 and December 31, 2002. The estimated average doses of radiation received by the ipsilateral lung/pleura range from 15.1 to 15.5 gray (Gy) based on the standard tangential (medial and lateral) and anterior supraclavicular treatment fields (that delivered a tumor dose of 40 to 50 Gy) used to treat breast cancer during the study period.
We found a significantly elevated risk of mesothelioma (standard incidence ratio [SIR] of 1.42; 95% CI, 1.02-1.94). Excesses began 10 years after a diagnosis of breast cancer, with the highest risk (SIR of 5.60; 95% CI, 2.05-12.21; 6 patients) observed at 30 years of follow-up, a temporal pattern that was consistent with the late effects of radiation. Risk was most pronounced for women diagnosed before 1970 (SIR of 2.46; 95% CI, 1.51-3.81; 20 cases). SIRs for the subset of 22 breast cancer patients reported to registries that record treatment data were 1.78 (95% CI, 1.00-2.95; 15 cases) for those who initially received radiotherapy compared with 0.95 (95% CI, 0.38-1.97; 7 cases) for whom radiotherapy was not recorded. Treatment regimens for breast cancer have undergone substantial changes over the past several decades, and therefore the evaluation of long-term survivors often reflects the effects of therapies that have subsequently been modified. Nonetheless, our findings add to the growing body of evidence that large doses of radiation might be associated with excess mesotheliomas, although analytic studies are required to establish a causal relation.