title: External validity of a trial comprised of elderly patients with hormone receptor-positive breast cancer.
abstract: BACKGROUND
  Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients.
  
  
  METHODS
  We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor-positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65-74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided.
  
  
  RESULTS
  Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population.
  
  
  CONCLUSIONS
  Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.
authors.affiliation: Affiliations of authors: Department of Surgical Oncology (WvdW, MK, EB, CJHvdV, GJL), Department of Gerontology and Geriatrics (WvdW, MK, EB, RGJW, AJMdC), and Department of Medical Oncology (JWRN), Leiden University Medical Center, Leiden, the Netherlands; Department of Research, Comprehensive Cancer Centre the Netherlands, Utrecht, the Netherlands (SS); Department of Health Technology and Services Research, University of Twente, Enschede, the Netherlands (SS); Department of Medical Oncology, Erasmus MC-Daniel Den Hoed Cancer Center, Rotterdam, the Netherlands (CS).
authors.forename: Willemien
authors.initials: W
authors.lastname: van de Water
authors.forename: Mandy
authors.initials: M
authors.lastname: Kiderlen
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.forename: Sabine
authors.initials: S
authors.lastname: Siesling
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Johan W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012042:Registries; D015203:Reproducibility of Results; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C056516:exemestane