Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: Risk factors for leukemia and myelodysplastic syndrome after breast cancer

Purpose To determine the risk factors for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after breast cancer. Patients and Methods We conducted a case-control study among women treated for breast cancer between 1985 and 2001 in French general hospitals, cancer centers, or clinics. We included 182 AML and MDS patients and 534 matched controls. Breast cancer characteristics, type of treatment, and family history of cancer were compared in both groups. Results The risk of AML/MDS was increased after topoisomerase-II inhibitor-based chemotherapy (P < 10(-16)) and was higher for mitoxantrone-based chemotherapy than for anthracycline-based chemotherapy (relative risk [RR] = 15.6; 95% Cl, 7.1 to 34.2; and RR = 2.7; 95% Cl, 1.7 to 4.5, respectively). After adjustment for other treatment components, the risk of AML/MDS in patients who received radiotherapy was multiplied by 3.9 ( 95% Cl, 1.4 to 10.8) but was not increased by alkylating agents. Patients receiving granulocyte colony-stimulating factor (G-CSF) support had an increased risk of AML/MDS (RR = 6.3; 95% Cl, 1.9 to 21), even when controlling for chemotherapy doses. Similar results were obtained when AML and MDS were considered separately. Conclusion This large case-control study demonstrates that the risk of AML/MDS is much higher with mitoxantrone-based chemotherapy than with anthracyclines-based chemotherapy in a population of women recently treated for breast cancer. The risk of AML/MDS associated with mitoxantrone must be kept in mind when using this drug to treat diseases other than breast cancer (eg, prostate cancer or multiple sclerosis). In addition, our study suggests the need to monitor the long-term effects of G-CSF therapy.