© The Author 2007. Published by Oxford University Press.
ARTICLE |
Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy
Affiliations of authors: Department of Medicine and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons (DH, AIN, VRG), and Departments of Epidemiology and Biostatistics, Mailman School of Public Health (DH, AIN, JSJ, JW, WYT, RM, VRG), Columbia University, New York, NY, Department of Statistics, National Cheng Kung University, Taiwan (WYT); Veterans Affairs Midwest Center for Health Services and Policy Research, Jesse Brown Veterans Affairs Medical Center (CLB); Division of Hematology and Oncology, Department of Medicine, and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (CLB)
Correspondence to: Dawn Hershman, MD, MS, Herbert Irving Comprehensive Cancer Center, 161 Ft Washington Ave., Rm. 1068, New York, NY 10032 (e-mail: dlh23{at}columbia.edu).
BACKGROUND: Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G-CSFs) or granulocyte–macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients.
METHODS: Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results–Medicare database who were diagnosed with stages I–III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided.
RESULTS: Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15).
CONCLUSIONS: The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free.
| CONTEXT AND CAVEATS Prior knowledge The cytokines granulocyte colony-stimulating factors (G-CSFs) and granulocyte macrophage colony stimulating factors (GM-CSFs) are used increasingly to avoid the myelosuppressive effects that would otherwise limit the chemotherapy dose in women with breast cancer. However, in vitro and epidemiologic evidence suggests that these cytokines may increase the risk of acute myelocytic leukemia (AML) or myelodysplastic syndrome (MDS). Study design Women included in a SEER–Medicare population-based database who received G-CSF or GM-CSF concurrently with chemotherapy for breast cancer were followed for the subsequent development of AML or MDS. Contribution Women with breast cancer who received either cytokine concurrently with chemotherapy had about a 2% risk of developing AML or MDS, whereas women who received chemotherapy alone had a subsequent AML or MDS risk of about 1%. Implications G-CSF and GM-CSF support may be associated with an increase in the risk of subsequent AML or MDS. However, the absolute risk was low, and the benefits may still outweigh any risks. Limitations The database includes only women 65 years of age and older, so the findings may not be generalizable to younger women. The claims data in the SEER—Medicare database may be incomplete. Information on dose and dose intensity was not available for individual women, and differences could have confounded the analysis. Additional studies will be required to determine whether the association is causal.
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Correspondence about this Article
- Re: Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy
- Matteo Clavarezza, Lucia Del Mastro, Paolo Pronzato, Paolo Bruzzi, and Marco Venturini
J Natl Cancer Inst 2007 99: 1050-1051.[Extract] [Full Text] [PDF]
- Re: Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy
- Joan L. Warren and Martin L. Brown
J Natl Cancer Inst 2007 99: 1050.[Extract] [Full Text] [PDF]
Editorial about this Article
- Granulocyte Colony-Stimulating Factor: Key (F)actor or Innocent Bystander in the Development of Secondary Myeloid Malignancy?
- Ivo P. Touw and Marijke Bontenbal
J Natl Cancer Inst 2007 99: 183-186.[Extract] [Full Text] [PDF]
Related Article in JNCI
- Press Release: Growth Factors Commonly Given With Chemotherapy Associated With Increased Risk of Blood Diseases
- Andrea Widener
J Natl Cancer Inst 2007 99: 181.[Extract] [Full Text]
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