Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer.
OBJECTIVE
To determine the risk factors for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after breast cancer.


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.


CONCLUSIONS
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.
Le Deley
Marie-Cécile
MC
Biostatistics and Epidemiology Unit, Department of Medicine, , Institut Gustave-Roussy, Villejuif, France. le_deley@igr.fr
Suzan
Florence
F
Cutuli
Bruno
B
Delaloge
Suzette
S
Shamsaldin
Akthar
A
Linassier
Claude
C
Clisant
Stéphanie
S
de Vathaire
Florent
F
Fenaux
Pierre
P
Hill
Catherine
C
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016022:Case-Control Studies; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000453:epidemiology; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000453:epidemiology; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology; D012307:Risk Factors
D018943:Anthracyclines; D000970:Antineoplastic Agents; D008942:Mitoxantrone