title: Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study.
abstract: BACKGROUND
  Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.
  
  
  METHODS
  We conducted a population-based, retrospective cohort study of 12,500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities.
  
  
  RESULTS
  Among 12 500 women (mean age = 60 years, range = 22-99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35).
  
  
  CONCLUSIONS
  Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.
authors.affiliation: Group Health Research Institute, 1730 Minor Ave, Ste 1600, Seattle, WA 98101, USA. bowles.e@ghc.org
authors.forename: Erin J Aiello
authors.initials: EJ
authors.lastname: Bowles
authors.forename: Robert
authors.initials: R
authors.lastname: Wellman
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
authors.forename: Adedayo A
authors.initials: AA
authors.lastname: Onitilo
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Freedman
authors.forename: Thomas
authors.initials: T
authors.lastname: Delate
authors.forename: Larry A
authors.initials: LA
authors.lastname: Allen
authors.forename: Larissa
authors.initials: L
authors.lastname: Nekhlyudov
authors.forename: Katrina A B
authors.initials: KA
authors.lastname: Goddard
authors.forename: Robert L
authors.initials: RL
authors.lastname: Davis
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.forename: Marianne Ulcickas
authors.initials: MU
authors.lastname: Yood
authors.forename: Catherine
authors.initials: C
authors.lastname: McCarty
authors.forename: David J
authors.initials: DJ
authors.lastname: Magid
authors.forename: Edward H
authors.initials: EH
authors.lastname: Wagner
mesh_terms: D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000068878:Trastuzumab
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab