Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment
10.1007/s10549-004-2472-8 Cite this article as: Rubino, C., Shamsaldin, A., Lê, M.G. et al. Breast Cancer Res Treat (2005) 89: 277. doi:10.1007/s10549-004-2472-8 Summary 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. Keywords bone sarcoma breast cancer case–control study cohort study dosimetry radiation secondary malignant neoplasm soft tissue sarcoma References Brady, MS, Garfein, CF, Petrek, JA, Brennan, MF 1994 Post-treatment sarcoma in breast cancer patients Ann Surg Oncol 1 66 72 PubMed Google Scholar Kim, JH, Chu, FC, Woodard, HQ, Melamed, MR, Huvos, A, Cantin, J 1978 Radiation-induced soft-tissue and bone sarcoma Radiology 129 501 508 PubMed Google Scholar Lagrange, JL, Ramaioli, A, Chateau, MC, Marchal, C, Resbeut, M, Richaud, P, Lagarde, P, Rambert, P, Tortechaux, J, Seng, SH, de la, FB, Reme-Saumon, M, Bof, J, Ghnassia, JP, Coindre, JM 2000 Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases Radiation Therapist and Pathologist Groups of the Federation Nationale des Centres de Lutte Contre le Cancer Radiology 216 197 205 PubMed Google Scholar Marchal, C, Weber, B, de Lafontan, B, Resbeut, M, Mignotte, H, du Chatelard, PP, Cutuli, B, Reme-Saumon, M, Broussier-Leroux, A, Chaplain, G, Lesaunier, F, Dilhuydy, JM, Lagrange, JL 1999 Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive Cancer Centers Int J Radiat Oncol Biol Phys 44 113 119 PubMed Google Scholar Cahan, WG, Woodard, HQ, Higinbotham, NL, Stewart, FW, Coley, BL 1948 Sarcoma arising in irradiated bone: report of eleven cases Cancer 1 3 29 PubMed Google Scholar Davis, FG, Boice, JD, Jr., Hrubec, Z, Monson, RR 1989 Cancer mortality in a radiation-exposed cohort of Massachusetts tuberculosis patients Cancer Res 49 6130 6136 PubMed Google Scholar Hawkins, MM, Wilson, LM, Burton, HS, Potok, MH, Winter, DL, Marsden, HB, Stovall, MA 1996 Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer J Natl Cancer Inst 88 270 278 PubMed Google Scholar Le Vu, B, de Vathaire, F, Shamsaldin, A, Hawkins, MM, Grimaud, E, Hardiman, C, Diallo, I, Vassal, G, Bessa, E, Campbell, S, Panis, X, Daly-Schveitzer, N, Lagrange, JL, Zucker, JM, Eschwege, F, Chavaudra, J, Lemerle, J 1998 Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood Int J Cancer 77 370 377 PubMed Google Scholar Nekolla, EA, Kreisheimer, M, Kellerer, AM, Kuse-Isingschulte, M, Gossner, W, Spiess, H 2000 Induction of malignant bone tumors in radium-224 patients: risk estimates based on the improved dosimetry Radiat Res 153 93 103 PubMed Google Scholar Tucker, MA, D’Angio, GJ, Boice, JD, Jr., Strong, LC, Li, FP, Stovall, M, Stone, BJ, Green, DM, Lombardi, F, Newton, W 1987 Bone sarcomas linked to radiotherapy and chemotherapy in children N Engl J Med 317 588 593 CrossRef PubMed Google Scholar Weiss, HA, Darby, SC, Doll, R 1994 Cancer mortality following X-ray treatment for ankylosing spondylitis Int J Cancer 59 327 338 PubMed Google Scholar Wong, FL, Boice, JD, Jr., Abramson, DH, Tarone, RE, Kleinerman, RA, Stovall, M, Goldman, MB, Seddon, JM, Tarbell, N, Fraumeni, JF, Jr., Li, FP 1997 Cancer incidence after retinoblastoma Radiation dose and sarcoma risk JAMA 278 1262 1267 PubMed Google Scholar
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