title: Initial versus sequential adjuvant aromatase inhibitor therapy: a review of the current data.
abstract: OBJECTIVE
  One of the principle unresolved questions in adjuvant endocrine therapy for breast cancer is whether it is more beneficial for women to receive aromatase inhibitor (AI) monotherapy or start with tamoxifen and then switch to AI therapy. This review will compare the current available efficacy, safety, and cost-effectiveness data for AIs in the initial adjuvant and switch adjuvant settings.
  
  
  METHODS
  A search of the Medline database from 1976 through 2006 was performed for the following terms: breast cancer, adjuvant, aromatase inhibitors, anastrozole, letrozole, exemestane, tamoxifen, sequential, switching. A search for relevant abstracts from the EBCC, ECCO, ASCO, and SABCS conferences was also performed.
  
  
  RESULTS
  In the upfront adjuvant setting, anastrozole and letrozole have both demonstrated a significant disease-free survival (DFS) benefit over tamoxifen. Upfront therapy with a nonsteroidal AI appears to be most critical for patients at risk of an early relapse, illustrated by the finding that upfront letrozole provided a significant early DFS advantage over tamoxifen only in patients with node-positive disease (hazard ratio = 0.71, p < 0.001). With respect to safety, both strategies have similar adverse event profiles. From an economic perspective, AIs, whether used upfront or sequentially, are considered cost-effective compared with tamoxifen due to the cost savings associated with a reduction in the breast cancer event rate. From the efficacy standpoint, modeling studies have produced inconsistent results and do not produce definitive data.
  
  
  CONCLUSIONS
  Differences in patient populations, definitions of end points, and prior tamoxifen usage between the trials discussed necessitates a careful interpretation but may provide insights in the treatment decision-making process. The BIG 1-98 trial was designed to compare letrozole monotherapy versus a letrozole-to-tamoxifen or reverse-sequence approach and should provide insights to the question of optimal therapy. Until results are available, for higher-risk patients (i.e., those with positive lymph nodes), initiation of treatment with a non-steroidal AI may be beneficial to avoid tamoxifen-associated early relapses that occur in the first 2 years after diagnosis.
authors.affiliation: Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO 63110, USA. mellis@im.wustl.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Caron E
authors.initials: CE
authors.lastname: Rigden
mesh_terms: D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000523:psychology; D003362:Cost-Benefit Analysis; D005260:Female; D017048:Health Care Costs; D006801:Humans; D009570:Nitriles / Q000627:therapeutic use; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; C056516:exemestane