title: Risk of acute leukemia following epirubicin-based adjuvant chemotherapy: a report from the National Cancer Institute of Canada Clinical Trials Group.
abstract: OBJECTIVE
  Cyclophosphamide, epirubicin, and fluorouracil (CEF), compared with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. has lead to an improvement in relapse-free and overall survival in premenopausal women with node-positive breast cancer. We undertook this analysis to more accurately define the estimate of risk of secondary acute leukemia (sAL) following epirubicin-containing chemotherapy regimens.
  
  
  METHODS
  We assessed the conditional probability of sAL among 1,545 women who received adjuvant (n = 1,477) or neoadjuvant (n = 68) chemotherapy in four National Cancer Institute of Canada Clinical Trials Group trials from 1990 to 1999. The risks associated with epirubicin-containing regimens (CEF or epirubicin and cyclophosphamide [EC]) and other regimens (doxorubicin and cyclophosphamide [AC] or CMF) were determined.
  
  
  RESULTS
  A total of 10 cases of sAL were observed (eight acute myelogeneous leukemia, two acute lymphoblastic leukemia): seven among women treated with CEF, two who had received AC, and one following CMF. Using competing risk statistics, the conditional probability of sAL was 1.7% (95% confidence interval [CI], 0.5 to 3.6) among 539 women treated with CEF chemotherapy at a follow-up of 8 years, 0.4% (95% CI, 0% to 1.3%) among the 678 who received CMF, and 1.3% (95% CI, 0% to 4.7%) among the 231 treated with AC. The conditional probability of death from breast cancer at 8 years for the entire group of women treated with epirubicin-containing regimens in all four trials was approximately 34.9%.
  
  
  CONCLUSIONS
  CEF chemotherapy for breast cancer carries a small increased risk of sAL compared with CMF. These estimates of acute leukemia risk are important in discussing treatment with women, especially patients with a lower risk of death from breast cancer, such as those with node-negative breast cancer.
authors.affiliation: Princess Margaret Hospital, 610 University Ave, Room 5-108, Toronto, Ontario, Canada M5G 2M9. michael.crump@uhn.on.ca
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
authors.forename: Vivien
authors.initials: V
authors.lastname: Bramwell
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pritchard
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000209:etiology*; D012306:Risk
chemical_list: D003561:Cytarabine; D015251:Epirubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate