title: Controversies in design and interpretation of adjuvant clinical trials.
abstract: Although aromatase inhibitors are widely used as adjuvant endocrine treatment for hormone-sensitive early breast cancer, the optimal treatment strategy is controversial. Differences in trial design, endpoint definitions, and patient populations preclude straightforward trial comparisons. Standardized, consistent endpoint definitions, focused on efficacy outcomes (e.g., time to recurrence, time to distant recurrence), would allow for more meaningful comparisons. Disease-free survival and overall survival should be secondary endpoints, since they include deaths without recurrence, which can dilute and confuse efficacy evaluations. Distant metastasis is an excellent surrogate for breast cancer death and is available a few years earlier. These changes should lead to more rapid and reliable introduction of improved therapeutic strategies.
authors.affiliation: Cancer Research UK, Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, UK. j.cuzick@qmul.ac.uk
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012107:Research Design; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen