title: Clinical validity/utility, change in practice patterns, and economic implications of risk stratifiers to predict outcomes for early-stage breast cancer: a systematic review.
abstract: BACKGROUND
  At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers.
  
  
  METHODS
  A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported.
  
  
  RESULTS
  Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications.
  
  
  CONCLUSIONS
  The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.
authors: Stanford University School of Medicine, Stanford, CA, USA. ujch@stanford.edu
authors: John
authors: J
authors: Hornberger
authors: Michael D
authors: MD
authors: Alvarado
authors: Chien
authors: C
authors: Rebecca
authors: Hialy R
authors: HR
authors: Gutierrez
authors: Tiffany M
authors: TM
authors: Yu
authors: William J
authors: WJ
authors: Gradishar
mesh_terms: D000912:Antibodies, Neoplasm / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000191:economics / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003362:Cost-Benefit Analysis; D019317:Evidence-Based Medicine; D005260:Female; D020869:Gene Expression Profiling; D017048:Health Care Costs; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010818:Practice Patterns, Physicians' / Q000191:economics / Q000639:trends; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor