title: Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511).
abstract: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines.
  
  
  
  We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS.
  
  
  
  On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS.
  
  
  
  We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA. rafreedman@partners.org.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Freedman
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic and Mayo Cancer Center, Rochester, MN, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Seisler
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic and Mayo Cancer Center, Rochester, MN, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Foster
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic and Mayo Cancer Center, Rochester, MN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Sloan
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Lafky
authors.affiliation: Duke University School of Medicine, Durham, NC, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Kimmick
authors.affiliation: Department of Medical Oncology and Therapeutics Research and Department of Population Sciences, City of Hope, Duarte, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hurria
authors.affiliation: Duke University School of Medicine, Durham, NC, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Cohen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Partridge
authors.affiliation: Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jatoi
authors.affiliation: Department of Hematology and Oncology, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: H D
authors.initials: HD
authors.lastname: Klepin
authors.affiliation: ProHEALTH Care Associates, Lake Success, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Citron
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Berry
authors.affiliation: Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: L N
authors.initials: LN
authors.lastname: Shulman
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: A U
authors.initials: AU
authors.lastname: Buzdar
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic and Mayo Cancer Center, Rochester, MN, USA.
authors.forename: V J
authors.initials: VJ
authors.lastname: Suman
authors.affiliation: Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Muss
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000209:etiology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000209:etiology*; D016609:Neoplasms, Second Primary; D012306:Risk; D013997:Time Factors
chemical_list: D018943:Anthracyclines
keywords: Breast cancer; Chemotherapy; Leukemia; Myelodysplastic syndrome; Older patients