title: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
abstract: BACKGROUND
  Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.
  
  
  METHODS
  This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy.
  
  
  RESULTS
  Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab.
  
  
  CONCLUSIONS
  One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)
authors.affiliation: Medicine Department, Jules Bordet Institute, Blvd. de Waterloo 125, 1000 Brussels, Belgium. martine.piccart@bordet.be
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart-Gebhart
authors.forename: Marion
authors.initials: M
authors.lastname: Procter
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Barrios
authors.forename: Günther
authors.initials: G
authors.lastname: Steger
authors.forename: Chiun-Shen
authors.initials: CS
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.forename: Moshe
authors.initials: M
authors.lastname: Inbar
authors.forename: Mikhail
authors.initials: M
authors.lastname: Lichinitser
authors.forename: István
authors.initials: I
authors.lastname: Láng
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nitz
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Christoph
authors.initials: C
authors.lastname: Thomssen
authors.forename: Caroline
authors.initials: C
authors.lastname: Lohrisch
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suter
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Tamás
authors.initials: T
authors.lastname: Suto
authors.forename: Victoria
authors.initials: V
authors.lastname: Greatorex
authors.forename: Carol
authors.initials: C
authors.lastname: Ward
authors.forename: Carolyn
authors.initials: C
authors.lastname: Straehle
authors.forename: Eleanor
authors.initials: E
authors.lastname: McFadden
authors.forename: M Stella
authors.initials: MS
authors.lastname: Dolci
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012008:Recurrence; D016019:Survival Analysis; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab