Increased risk of acute leukemia after adjuvant chemotherapy for breast cancer: A population-based study

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 Cote 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 war obtained from records of cancer registries their 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 greater than or equal to 13 mg/m(2). 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 lass leukemogenic than mitoxantrone and could be preferred in an adjuvant setting. J Clin Oncol 18:2836-2842. (C) 2000 by American Society of Clinical Oncology.