Secondary leukemia after epirubicin-based adjuvant chemotherapy in operable breast cancer patients:: 16 years experience of the French Adjuvant Study Group

Background: The purpose of this study was to evaluate incidence and risk factors of secondary leukemia after adjuvant epirubicin-based chemotherapy in breast cancer patients. Patients and methods: Among eight French Adjuvant Study Group trials, 3653 patients were assessable: 2603 received epirubicin; 682 received hormonotherapy; and 368 had no systemic treatment. Chemotherapy was FEC regimen in 85% of cases (fluorouracil 500 mg/m(2), epirubicin 50, 75 or 100 mg/m(2), cyclophosphamide 500 mg/m(2), three or six cycles). Epirubicin cumulative dose was <300 mg/m(2) in 1045 patients; 300-600 mg/m(2) in 1187; and >= 600 mg/m(2) in 286, followed by radiotherapy in 96% of cases. The median follow-up was 104 months. Results: Eight cases of leukemia occurred in epirubicin-exposed patients and one in non-exposed patients. After 9 years, the risk of developing a leukemia was 0.34% (95% confidence interval 0.11-0.57) in epirubicin-exposed patients. In patients receiving chemotherapy, leukemia subtypes were: AML2 (two), AML3 (one), AML4 (three) and ALL (two). None of the classically recognized risk factors was significantly correlated with the occurrence of a leukemia. Conclusion: Irrespective of the dose, the incidence of secondary leukemia after adjuvant epirubicin-based chemotherapy was low. After a long follow-up, the benefit/risk ratio for early breast cancer patients remained in favor of epirubicin-based adjuvant chemotherapy: eight cases (0.31%) occurred, and in some of them, treatment causality could be debatable.