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Increased Risk of Acute Leukemia After Adjuvant Chemotherapy for Breast Cancer: A Population-Based Study

From the Registre des Cancers Gynécologiques de Côte d’Or, Faculté de Médecine; Centre d’Epidémiologie de Population de l’Université de Bourgogne, Faculté de Médecine; Centre Régional de Pharmacovigilance, Centre Hospitalier et Universitaire; and Registre des Hémopathies Malignes de Côte d’Or, Faculté de Médecine, Dijon, France.

Address reprint requests to Claire Bonithon-Kopp, MD, PhD, Centre d’Epidémiologie de Population de l’Université de Bourgogne, Faculté de Médecine, 7 bd Jeanne d’Arc, 21,033 Dijon Cedex, France; email bonithon{at}u-bourgogne.fr

PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors.

PATIENTS AND METHODS: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Côte d’Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area.

RESULTS: Until December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P < .0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses 13 mg/m².

CONCLUSION: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.

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