Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment

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Abstract
Background. To quantify the risk of soft tissue and bone sarcomas after breast cancer according to the doses and technical modalities of irradiation. Methods. We followed a cohort of 6597 breast-cancer patients for 8.3 years on average. The number of soft tissue and bone sarcomas was compared to the expected number based on the incidence rates in the general French population. We also estimated the risk of sarcoma according to the radiation dose received at site of the sarcoma in a nested case control study of 14 breast-cancer patients who subsequently developed a sarcoma and 98 controls matched for age at diagnosis of breast cancer, period of initial treatment and length of follow-up. Results. In the cohort-study, 12 women who had initially received radiotherapy treatment developed a bone or soft tissue sarcoma during the follow-up period. The expected number of cases during this period was 1.7 (SIR=7.0, 95% CI: 3.7–11.7) and the mean annual excess incidence during the same period was 21 per 100,000 person-years. The 15-year cumulative incidence of sarcoma was 0.28% (95% CI: 0.10–0.45%). In the case–control study, all the 14 cases had received at least 11.8 Gray at the site of the sarcoma, which was always located in the irradiated field or in the upper ipsilateral extremity of the arm. A dose–effect relationship was observed (p < 0.001). The best fit was obtained for a quadratic dose–response relationship, without a negative exponential term for cell killing at high doses. The risk of sarcoma was 30.6 higher for doses of more than 44 Gray than for doses of less than 15 Gray. Conclusions. High doses of radiation strongly increase the risk of bone and soft tissue sarcoma.