title: Challenges in breast cancer clinical trial design in the postgenomic era.
abstract: OBJECTIVE
  Clinical trials in breast cancer (BC) have seldom taken into consideration molecular heterogeneity, because most have been performed in unselected populations. Hence, their results provide an estimated average benefit for the entire BC population, which may not always be translated to subsets of patients with certain characteristics, let alone to individual patients. Further understanding and acknowledgment of heterogeneity is vital for the development of individualized therapy in BC. New approaches are needed for trial design, patient selection, and choice of endpoints (including surrogate markers). The neoadjuvant setting presents a unique opportunity to test new concepts in a previously untreated patient population, because they may yield preliminary answers in a shorter time than that required in adjuvant trials.
  
  
  RESULTS
  The importance of patient selection in the development of targeted agents is exemplified by trastuzumab in BC and of gefitinib in lung cancer. Ongoing innovative trials that investigate biologic hypotheses include the BIG-EORTC p53, TOP and FRAGRANCE trials (which study predictive factors for response), and the NNBC-3 and MINDACT trials (which study prognostic factors).
  
  
  CONCLUSIONS
  There is an urgent need to break from traditional clinical development and to incorporate new molecular knowledge and translational research in the design of clinical trials. The success of new approaches in BC research critically depends on well-conducted translational research linked to prospective clinical trials, and international collaboration, bringing together human and technological resources.
authors.affiliation: Translational Research Unit, Jules Bordet Institute, 121 Boulevard de Waterloo, Brussels 1000, Belgium.
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003663:Decision Trees; D005260:Female; D016045:Human Genome Project; D006801:Humans; D012107:Research Design