title: 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.
abstract: BACKGROUND
  Trastuzumab--a humanised monoclonal antibody against HER2--has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study.
  
  
  METHODS
  HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11.
  
  
  RESULTS
  97 (5.7%) patients randomised to observation alone and 58 (3.4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0.66 (95% CI 0.47-0.91; p=0.0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 (0.54-0.76; p<0.0001).
  
  
  CONCLUSIONS
  Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.
authors.affiliation: Royal Marsden Hospital, London, UK. ian.smith@rmh.nhs.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Marion
authors.initials: M
authors.lastname: Procter
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Sébastien
authors.initials: S
authors.lastname: Guillaume
authors.forename: Andrea
authors.initials: A
authors.lastname: Feyereislova
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mariani
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardley
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.forename: Roberto I
authors.initials: RI
authors.lastname: Lopez
authors.forename: Peter
authors.initials: P
authors.lastname: Mallmann
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wilcken
authors.forename: Erik
authors.initials: E
authors.lastname: Wist
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez Rovira
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart-Gebhart
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab