Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment Article DOI:
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
UNSCEAR. Sources and Effects of Ionizing Radiation. United Nations, New York, NY, USA, 2000.
Harvey, EB, Brinton, LA 1985 Second cancer following cancer of the breast in Connecticut, 1935–82 Natl Cancer Inst Monogr 68 99 112 PubMed Google Scholar Huang, J, Mackillop, WJ 2001 Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma Cancer 92 172 180 PubMed Google Scholar Yap, J, Chuba, PJ, Thomas, R, Aref, A, Lucas, D, Severson, RK, Hamre, M 2002 Sarcoma as a second malignancy after treatment for breast cancer Int J Radiat Oncol Biol Phys 52 1231 1237 PubMed Google Scholar Karlsson, P, Holmberg, E, Johansson, KA, Kindblom, LG, Carstensen, J, Wallgren, A 1996 Soft tissue sarcoma after treatment for breast cancer Radiother Oncol 38 25 31 PubMed Google Scholar Karlsson, P, Holmberg, E, Samuelsson, A, Johansson, KA, Wallgren, A 1998 Soft tissue sarcoma after treatment for breast cancer–a Swedish population-based study Eur J Cancer 34 2068 2075 PubMed Google Scholar Taghian, A, de Vathaire, F, Terrier, P, Le, M, Auquier, A, Mouriesse, H, Grimaud, E, Sarrazin, D, Tubiana, M 1991 Long-term risk of sarcoma following radiation treatment for breast cancer Int J Radiat Oncol Biol Phys 21 361 367 PubMed Google Scholar Rubino, C, de Vathaire, F, Diallo, I, Shamsaldin, A, Le, MG 2000 Increased risk of second cancers following breast cancer: role of the initial treatment Breast Cancer Res Treat 61 183 195 PubMed Google Scholar Diallo, I, Lamon, A, Shamsaldin, A, Grimaud, E, de Vathaire, F, Chavaudra, J 1996 Estimation of the radiation dose delivered to any point outside the target volume per patient treated with external beam radiotherapy Radiother Oncol 38 269 271 PubMed Google Scholar Grimaud, E, Shamsaldin, A, Lamon, A 1994 Programme original de calcul de dose applique a l’étude de seconds cancers, sfro 5éme Congrés, Paris, France Bull Cancer/Radiother 81 482 Google Scholar Shamsaldin, A, Grimaud, E, Diallo, I, Hardiman, C, de Vathaire, F, Chavaudra, J 1997 Knowledge of doses from external radiotherapy for a cancer in childhood IAEA Tech Doc 976 94 97 Google Scholar Shamsaldin, A, Grimaud, E, Hardiman, C, Diallo, I, de Vathaire, F, Chavaudra, J 1998 Dose distribution throughout the body from radiotherapy for Hodgkin’s disease in childhood Radiother Oncol 49 85 90 PubMed Google Scholar
Shamsaldin A, Grimaud E, Ligot L, Diallo I, de Vathaire F, Chavaudra J: Theoretical Models for Retrospective Dosimetry, IRPA10, Japan. Proceedings p-3a-208: 1-6, 2000
de Vathaire, F, Koscielny, S, Rezvani, A, Laplanche, A, Estève, J, Ferlay, J 1996Estimation de l’incidence des cancers en France: période 1983–1987. Les Editions INSERM Paris, France Google Scholar Breslow, NE, Day, NE 1987 Statistical methods in cancer research Volume II–The design and analysis of cohort studies IARC Sci Publ (82) 1 406 Google Scholar
Preston DL, Lubin JH, Pierce DA, McConney ME: EPICURE. Generalized Regression Models for Epidemiological Data. Hirosoft International Corporation Seattle, WA, 1991.
Moolgavkar, SH, Venzon, DJ 1987 A method for computing profile likelihood-based confidence bounds Ann Statist 15 346 359 Google Scholar
Breslow NE, Day NE: Statistical methods in cancer research. Volume I - The analysis of case-control studies. IARC Sci Publ (32): 5-338, 1980
Doherty, MA, Rodger, A, Langlands, AO, Kerr, GR 1993 Multiple primary tumours in patients treated with radiotherapy for breast cancer Radiother Oncol 26(2): 125-131 26 125 131 Google Scholar Evans, HS, Lewis, CM, Robinson, D, Bell, CM, Moller, H, Hodgson, SV 2001 Incidence of multiple primary cancers in a cohort of women diagnosed with breast cancer in southeast England Br J Cancer 84 435 440 PubMed Google Scholar Ewertz, M, Mouridsen, HT 1985 Second cancer following cancer of the female breast in Denmark, 1943–80 Natl Cancer Inst Monogr 68 325 329 PubMed Google Scholar Schottenfeld, D, Berg, J 1971 Incidence of miltiple primary cancers IV. Cancers of the female breast and genital organs J Natl Cancer Inst 46 161 170 PubMed Google Scholar Volk, N, Pompe-Kirn, V 1997 Second primary cancers in breast cancer patients in Slovenia Cancer Causes Control 8 764 770 PubMed Google Scholar Lavey, RS, Eby, NL, Prosnitz, LR 1990 Impact of radiation therapy and/or chemotherapy on the risk for a second malignancy after breast cancer Cancer 66 874 881 PubMed Google Scholar Valagussa, P, Moliterni, A, Terenziani, M, Zambetti, M, Bonadonna, G 1994 Second malignancies following CMF-based adjuvant chemotherapy in resectable breast cancer Ann Oncol 5 803 808 PubMed Google Scholar Coleman, MP, Esteve, J, Damiecki, P, Arslan, A, Renard, H 1993 Trends in cancer incidence and mortality IARC Sci Publ 121 1 806 PubMed Google Scholar
Storm HH: Cancers of the soft tissues. Cancer Surv 19-20: 197-217, 1994
Google Scholar Doherty, MA, Rodger, A, Langlands, AO 1986 Sarcoma of bone following therapeutic irradiation for breast carcinoma Int J Radiat Oncol Biol Phys 12 103 106 PubMed Google Scholar Pierce, SM, Recht, A, Lingos, TI, Abner, A, Vicini, F, Silver, B, Herzog, A, Harris, JR 1992 Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer Int J Radiat Oncol Biol Phys 23 915 923 PubMed Google Scholar Hatfield, PM, Schulz, MD 1970 Postirradiation sarcoma Including 5 cases after X-ray therapy of breast carcinoma. Radiology 96 593 602 Google Scholar
UNSCEAR. Sources and Effects of Ionizing Radiation. United Nations, New York, NY, USA, 2000.
Boice, JD, Jr, Engholm, G, Kleinerman, RA, Blettner, M, Stovall, M, Lisco, H, Moloney, WC, Austin, DF, Bosch, A, Cookfair, DL 1988 Radiation dose and second cancer risk in patients treated for cancer of the cervix Radiat Res 116 3 55 PubMed Google Scholar Gorodetsky, R, Lotan, C, Piggot, K, Pierce, LJ, Polyansky, I, Dische, S, Saunders, M, Lichter, AS, Vexler, A 1999 Late effects of dose fractionation on the mechanical properties of breast skin following post-lumpectomy radiotherapy Int J Radiat Oncol Biol Phys 45 893 900 PubMed Google Scholar Whelan, T, MacKenzie, R, Julian, J, Levine, M, Shelley, W, Grimard, L, Lada, B, Lukka, H, Perera, F, Fyles, A, Laukkanen, E, Gulavita, S, Benk, V, Szechtman, B 2002 Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer J Natl Cancer Inst 94 1143 1150 PubMed Google Scholar Li FP, Fraumeni, JF, Jr 1969 Soft-tissue sarcomas, breast cancer, and other neoplasms A familial syndrome? Ann Intern Med 71 747 752 Google Scholar Venkitaraman, AR 2001 Functions of BRCA1 and BRCA2 in the biological response to DNA damage J Cell Sci 114 3591 3598 PubMed Google Scholar Petrek, JA, Heelan, MC 1998 Incidence of breast carcinoma-related lymphedema Cancer 83 2776 2781 PubMed Google Scholar Meek, AG 1998 Breast radiotherapy and lymphedema Cancer 83 2788 2797 PubMed Google Scholar Johansson, S, Svensson, H, Denekamp, J 2002 Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients Int J Radiat Oncol Biol Phys 52 1207 1219 PubMed Google Scholar Arriagada, R, Mouriesse, H, Rezvani, A, Sarrazin, D, Clark, RM, DeBoer, G, Bush, RS 1993 Radiotherapy alone in breast cancer Analysis of tumor and lymph node radiation doses and treatment-related complications. The experience of the Gustave-Roussy Institute and the Princess Margaret Hospital Radiother Oncol 27 1 6 PubMed Google Scholar Stewart, FW, Treves, N 1981 Classics in oncology: lymphangiosarcoma in postmastectomy lymphedema: a report of six cases in elephantiasis chirurgica CA Cancer J Clin 31 284 299 PubMed Google Scholar Body, G, Sauvanet, E, Calais, G, Fignon, A, Fetissof, F, Lansac, J 1987 Cutaneous angiosarcoma of the breast following surgery and irradiation of breast adenocarcinoma J Gynecol Obstet Biol Reprod (Paris) 16 479 483 Google Scholar Strobbe, LJ, Peterse, HL, van Tinteren, H, Wijnmaalen, A, Rutgers, EJ 1988 Angiosarcoma of the breast after conservation therapy for invasive cancer, the incidence and outcome. An unforseen sequela Breast Cancer Res Treat 47 101 109 Google Scholar