Therapy-related acute leukemia in breast cancer patients: twelve cases treated with a topoisomerase inhibitor

BACKGROUND Therapy-related myeloid neoplasm (t-MN) is a distinct class of acute myeloid leukemia (AML) in the World Health Organization (WHO) classification. Both AML and acute lymphoblastic leukemia (ALL) may develop after treatment for primary cancer. Topoisomerase inhibitors are commonly used to treat breast cancer patients and are well-known for their effect on leukemogenesis of therapy-related acute leukemias (t-AL). METHODS We retrospectively evaluated bone marrow test results, chromosomal findings, and clinical characteristics of 12 patients who received topoisomerase inhibitors for breast cancer treatment and later developed acute leukemia. RESULTS Fourteen patients (0.2%) developed t-AL after treatment for breast cancer. Topoisomerase inhibitors were administered to 12 patients. Among them, 9 patients (75%, 9/12) were diagnosed with therapy-related AML (t-AML) and 3 patients (25%, 3/12) with therapy-related ALL (t-ALL). Eight patients (67%, 8/12) showed translocation involving 11q23 and 3 different partner genes, 19p13.1 (37.5%, 3/8), 9p22 (37.5%, 3/8), and 4q21 (25%, 2/8). The median interval between completion of chemotherapy for breast cancer and occurrence of t-AL was 25 months. Patients with 11q23 translocation showed markedly poorer event-free survival than the group without involvement of 11q23. CONCLUSION The incidence rate of t-AL after treatment for breast cancer was 0.2% in a tertiary hospital in Korea. Translocation involving the MLL gene was frequently found in t-AL caused by a topoisomerase inhibitor and was related to poor prognosis.