title: Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31.
abstract: OBJECTIVE
  Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited.
  
  
  METHODS
  Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis.
  
  
  RESULTS
  At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm (P < .001). Similarly, there continues to be a statistically significant 39% reduction in death rate in favor of the trastuzumab-containing arm (P < .001).
  
  
  CONCLUSIONS
  These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date. The clinical benefits continue to outweigh the risks of adverse effects.
authors.affiliation: Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Edward H
authors.initials: EH
authors.lastname: Romond
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Jong-Hyeon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab