title: Myelodysplastic syndrome and acute myeloid leukemia following adjuvant chemotherapy with and without granulocyte colony-stimulating factors for breast cancer.
abstract: Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. We conducted a retrospective cohort study of women aged ≥66 years with stage I-III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy, and/or G-CSF. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for MDS/AML risk. Among 56,251 breast cancer cases, 1.2 % developed MDS/AML during median follow-up of 3.2 years. 47.1 % of women received radiation and 14.3 % received chemotherapy. Compared to breast cancer cases treated with surgery alone, those treated with chemotherapy (HR = 1.38, 95 %-CI 0.98-1.93) and chemotherapy/radiation (HR = 1.77, 95 %-CI 1.25-2.51) had increased risk of MDS/AML, but not radiation alone (HR = 1.08, 95 % CI 0.86-1.36). Among chemotherapy regimens and G-CSF, MDS/AML risk was differentially associated with anthracycline/cyclophosphamide-containing regimens (HR = 1.86, 95 %-CI 1.33-2.61) and filgrastim (HR = 1.47, 95 %-CI 1.05-2.06), but not pegfilgrastim (HR = 1.10, 95 %-CI 0.73-1.66). We observed increased MDS/AML risk among older breast cancer survivors treated with anthracycline/cyclophosphamide chemotherapy that was enhanced by G-CSF. Although small, this risk warrants consideration when determining adjuvant chemotherapy and neutropenia prophylaxis for breast cancer patients.
authors.affiliation: Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, 833 South Wood Street M/C 871, Chicago, IL, 60612-7230, USA. gcalip@uic.edu.|Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. gcalip@uic.edu.|Department of Epidemiology, University of Washington, Seattle, WA, USA. gcalip@uic.edu.
authors.forename: Gregory S
authors.identifier: http://orcid.org/0000-0002-7744-3518
authors.initials: GS
authors.lastname: Calip
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.|HealthStat Consulting, Inc., Seattle, WA, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Malmgren
authors.affiliation: Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, 833 South Wood Street M/C 871, Chicago, IL, 60612-7230, USA.
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.affiliation: Swedish Cancer Institute, Seattle, WA, USA.
authors.forename: Henry G
authors.initials: HG
authors.lastname: Kaplan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000473:pathology*; D009367:Neoplasm Staging; D011092:Polyethylene Glycols; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D000069585:Filgrastim
keywords: Acute myeloid leukemia; Adjuvant chemotherapy; Breast cancer; Granulocyte colony-stimulating factors; Myelodysplastic syndrome