Originally published as JCO Early Release 10.1200/JCO.2006.05.9048 on December 11 2006

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Anthracyclines, Mitoxantrone, Radiotherapy, and Granulocyte Colony-Stimulating Factor: Risk Factors for Leukemia and Myelodysplastic Syndrome After Breast Cancer

Marie-Cécile Le Deley, Florence Suzan, Bruno Cutuli, Suzette Delaloge, Akthar Shamsaldin, Claude Linassier, Stéphanie Clisant, Florent de Vathaire, Pierre Fenaux, Catherine Hill

From the Biostatistics and Epidemiology Unit, Department of Medicine, Radiophysics Unit, Hematology Unit, and Cytogenetics Laboratory, Institut Gustave-Roussy; L'Institut National de la Santé et de la Recherche Médicale Unit 605, Villejuif; Clinique de Courlancy, Reims; Hôpital Bretonneau, Tours; and the Hematology Department, Hôpital Avicenne, Paris XIII University, Bobigny, France

Address reprint requests to Marie-Cécile Le Deley, MD, PhD, Service de Biostatistique et d'Epidémiologie, Institut Gustave-Roussy, rue Camille Desmoulins, 94805 Villejuif, France; e-mail: le_deley{at}igr.fr

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% CI, 7.1 to 34.2; and RR = 2.7; 95% CI, 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% CI, 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% CI, 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.

published online ahead of print at www.jco.org on December 11, 2006.

Supported by the Institut Gustave-Roussy, the Fondation de France (Comité Leucémies), the Association pour la Recherche sur le Cancer, and Wyeth Laboratory, France.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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