title: Disease-related outcomes with long-term follow-up: an updated analysis of the intergroup exemestane study.
abstract: OBJECTIVE
  Intergroup Exemestane Study (IES), an investigator-led study in 4,724 postmenopausal patients with early-stage breast cancer has demonstrated clinically important benefits from switching adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane. Now, with longer follow-up, a large number of non-breast cancer-related events have been reported. Exploratory analyses describe breast cancer-free survival (BCFS) and explore incidence and patterns of the different competing events.
  
  
  METHODS
  Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years of adjuvant endocrine therapy. At this planned analysis, the median follow-up was 91 months. Principal analysis focuses on 4,052 patients with estrogen receptor (ER) -positive and 547 with ER-unknown tumors.
  
  
  RESULTS
  In all, 930 BCFS events have been reported (exemestane, 423; tamoxifen, 507), giving an unadjusted hazard ratio (HR) of 0.81 (95% CI, 0.71 to 0.92; P = .001) in favor of exemestane in the ER-positive/ER unknown group. Analysis partitioned at 2.5 years after random assignment showed that the on-treatment benefit of switching to exemestane (HR, 0.60; 95% CI, 0.48 to 0.75; P < .001) was not lost post-treatment, but that there was no additional gain once treatment had ceased (HR, 0.94; 95% CI, 0.80 to 1.10; P = .60). Improvement in overall survival was demonstrated, with 352 deaths in the exemestane group versus 405 deaths in the tamoxifen group (HR, 0.86; 95% CI, 0.75 to 0.99; P = .04). Of these, 222 were reported as intercurrent deaths (exemestane, 107; tamoxifen, 115).
  
  
  CONCLUSIONS
  The protective effect of switching to exemestane compared with continuing on tamoxifen on risk of relapse or death was maintained for at least 5 years post-treatment and was associated with a continuing beneficial impact on overall survival.
authors: The Institute of Cancer Research, Sutton, UK. Judith.Bliss@icr.ac.uk
authors: Judith M
authors: JM
authors: Bliss
authors: Lucy S
authors: LS
authors: Kilburn
authors: Robert E
authors: RE
authors: Coleman
authors: John F
authors: JF
authors: Forbes
authors: Alan S
authors: AS
authors: Coates
authors: Stephen E
authors: SE
authors: Jones
authors: Jacek
authors: J
authors: Jassem
authors: Thierry
authors: T
authors: Delozier
authors: Jørn
authors: J
authors: Andersen
authors: Robert
authors: R
authors: Paridaens
authors: Cornelis J H
authors: CJ
authors: van de Velde
authors: Per E
authors: PE
authors: Lønning
authors: James
authors: J
authors: Morden
authors: Justine
authors: J
authors: Reise
authors: Laura
authors: L
authors: Cisar
authors: Thomas
authors: T
authors: Menschik
authors: R Charles
authors: RC
authors: Coombes
mesh_terms: D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; C056516:exemestane