title: Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer.
abstract: OBJECTIVE
  To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome.
  
  
  METHODS
  A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided.
  
  
  RESULTS
  When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor-positive, human epidermal growth factor receptor 2-nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death.
  
  
  CONCLUSIONS
  Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor-positive disease.
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA. jsparano@montefiore.org.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Ligibel
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Tom
authors.initials: T
authors.lastname: Saphner
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
authors.affiliation: Joseph A. Sparano, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Fengmin Zhao and Jennifer A. Ligibel, Dana-Farber Cancer Institute-Harvard University, Boston, MA; Silvana Martino, John Wayne Cancer Institute, Santa Monica, CA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Tom Saphner, Vince Lombardi Cancer Center, Two Rivers, WI; Antonio C. Wolff, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; George W. Sledge Jr, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; William C. Wood, Winship Cancer Center, Emory University, Atlanta, GA; and Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009367:Neoplasm Staging; D009765:Obesity / Q000150:complications / Q000208:ethnology; D017239:Paclitaxel / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel