Breast Cancer and Other Second Neoplasms after Childhood Hodgkin's Disease
Smita Bhatia, M.D., M.P.H., Leslie L. Robison, Ph.D., Odile Oberlin, M.D., Mark Greenberg, M.B., Ch.B., Greta Bunin, Ph.D., Franca Fossati-Bellani, M.D., and Anna T. Meadows, M.D.
Background Patients who survive Hodgkin's disease are at increasedrisk for second neoplasms. As survival times increase, solidtumors are emerging as a serious long-term complication.
Methods The Late Effects Study Group followed a cohort of 1380children with Hodgkin's disease to determine the incidence ofsecond neoplasms and the risk factors associated with them.
Results In this cohort, there were 88 second neoplasms as comparedwith 4.4 expected in the general population (standardized incidenceratio, 18.1; 95 percent confidence interval, 14.3 to 22.3).The estimated actuarial incidence of any second neoplasm 15years after the diagnosis of Hodgkin's disease was 7.0 percent(95 percent confidence interval, 5.2 to 8.8 percent); the incidenceof solid tumors was 3.9 percent (95 percent confidence interval,2.3 to 5.5 percent). Breast cancer was the most common solidtumor (standardized incidence ratio, 75.3; 95 percent confidenceinterval, 44.9 to 118.4), with an estimated actuarial incidencein women that approached 35 percent (95 percent confidence interval,17.4 to 52.6 percent) by 40 years of age. Older age (10 to 16vs. <10 years) at the time of radiation treatment (relativerisk, 1.9) and a higher dose (2000 to 4000 vs. <2000 cGy)of radiation (relative risk, 5.9) were associated with significantlyincreased risk of breast cancer. The estimated actuarial incidenceof leukemia reached a plateau of 2.8 percent (95 percent confidenceinterval, 0.8 to 4.8 percent) 14 years after diagnosis. Treatmentwith alkylating agents, older age at the diagnosis of Hodgkin'sdisease, recurrence of Hodgkin's disease, and a late stage ofdisease at diagnosis were risk factors for leukemia.
Conclusions The risk of solid tumors, especially breast cancer,is high among women who were treated with radiation for childhoodHodgkin's disease. Systematic screening for breast cancer couldbe important in the health care of such women.
Source Information
From the Department of Pediatrics, University of Minnesota, Minneapolis (S.B., L.L.R.); the Institut Gustave-Roussy, Villejuif, France (O.O.); the Hospital for Sick Children, Toronto (M.G.); the Children's Hospital of Philadelphia, Philadelphia (G.B., A.T.M.); and the National Tumor Institute, Milan, Italy (F.F.-B.).
Address reprint requests to Dr. Robison at the Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Box 422 UMHC, Minneapolis, MN 55455.
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(2001). Early-Stage Hodgkin's Disease: To Mantle or Not to Mantle?. JCO
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Seidemann, K., Tiemann, M., Schrappe, M., Yakisan, E., Simonitsch, I., Janka-Schaub, G., Dorffel, W., Zimmermann, M., Mann, G., Gadner, H., Parwaresch, R., Riehm, H., Reiter, A.
(2001). Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood
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(2001). Low-Dose Radiation Is Sufficient for the Noninvolved Extended-Field Treatment in Favorable Early-Stage Hodgkin's Disease: Long-Term Results of a Randomized Trial of Radiotherapy Alone. JCO
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(2001). Second Malignant Neoplasms in Five-Year Survivors of Childhood Cancer: Childhood Cancer Survivor Study. JNCI J Natl Cancer Inst
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Bhatia, S., Louie, A. D., Bhatia, R., O'Donnell, M. R., Fung, H., Kashyap, A., Krishnan, A., Molina, A., Nademanee, A., Niland, J. C., Parker, P. A., Snyder, D. S., Spielberger, R., Stein, A., Forman, S. J.
(2001). Solid Cancers After Bone Marrow Transplantation. JCO
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Behrens, C., Travis, L. B., Wistuba, I. I., Davis, S., Maitra, A., Clarke, E. A., Lynch, C. F., Glimelius, B., Wiklund, T., Tarone, R., Gazdar, A. F.
(2000). Molecular Changes in Second Primary Lung and Breast Cancers after Therapy for Hodgkin's Disease. Cancer Epidemiol. Biomarkers Prev.
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(2000). Abnormalities of the Thyroid in Survivors of Hodgkin's Disease: Data from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab.
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Martin, A.-M., Weber, B. L.
(2000). Genetic and Hormonal Risk Factors in Breast Cancer. JNCI J Natl Cancer Inst
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Metayer, C., Lynch, C. F., Clarke, E. A., Glimelius, B., Storm, H., Pukkala, E., Joensuu, T., van Leeuwen, F. E., van't Veer, M. B., Curtis, R. E., Holowaty, E. J., Andersson, M., Wiklund, T., Gospodarowicz, M., Travis, L. B.
(2000). Second Cancers Among Long-Term Survivors of Hodgkin's Disease Diagnosed in Childhood and Adolescence. JCO
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Krishnan, A., Bhatia, S., Slovak, M. L., Arber, D. A., Niland, J. C., Nademanee, A., Fung, H., Bhatia, R., Kashyap, A., Molina, A., O'Donnell, M. R., Parker, P. A., Sniecinski, I., Snyder, D. S., Spielberger, R., Stein, A., Forman, S. J.
(2000). Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood
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Reiter, A., Schrappe, M., Ludwig, W.-D., Tiemann, M., Parwaresch, R., Zimmermann, M., Schirg, E., Henze, G., Schellong, G., Gadner, H., Riehm, H.
(2000). Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM Group report. Blood
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Socie, G., Curtis, R. E., Deeg, H. J., Sobocinski, K. A., Filipovich, A. H., Travis, L. B., Sullivan, K. M., Rowlings, P. A., Kingma, D. W., Banks, P. M., Travis, W. D., Witherspoon, R. P., Sanders, J., Jaffe, E. S., Horowitz, M. M.
(2000). New Malignant Diseases After Allogeneic Marrow Transplantation for Childhood Acute Leukemia. JCO
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(1999). Heterozygous Germline ATM Mutations Do Not Contribute to Radiation-Associated Malignancies After Hodgkin's Disease. JCO
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