title: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
abstract: BACKGROUND
  We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer.
  
  
  METHODS
  The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel.
  
  
  RESULTS
  By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831.
  
  
  CONCLUSIONS
  Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 and NCT00005970.)
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Romond
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: John
authors.initials: J
authors.lastname: Bryant
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tan-Chiu
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pisansky
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Leila A
authors.initials: LA
authors.lastname: Kutteh
authors.forename: Victor G
authors.initials: VG
authors.lastname: Vogel
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.forename: Greg
authors.initials: G
authors.lastname: Yothers
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Ann M
authors.initials: AM
authors.lastname: Brown
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Wilma L
authors.initials: WL
authors.lastname: Lingle
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Klein
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012008:Recurrence; D016019:Survival Analysis; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C010013:adriamycinol