Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials Review uri icon


MeSH Major

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Biomarkers, Tumor
  • Breast Neoplasms
  • Neoadjuvant Therapy


  • Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy "curable" disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a "cell cycle response" is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials.

publication date

  • May 2005



  • Review



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.jsbmb.2005.04.017

PubMed ID

  • 15994076

Additional Document Info

start page

  • 91

end page

  • 5


  • 95


  • 1-5