External validity of a trial comprised of elderly patients with hormone receptor-positive breast cancer

J Natl Cancer Inst. 2014 Apr;106(4):dju051. doi: 10.1093/jnci/dju051. Epub 2014 Mar 19.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstadienes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Netherlands / epidemiology
  • Odds Ratio
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Registries
  • Reproducibility of Results
  • Tamoxifen / administration & dosage
  • Treatment Outcome


  • Androstadienes
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • exemestane