title: A Prospective Comparison of the 21-Gene Recurrence Score and the PAM50-Based Prosigna in Estrogen Receptor-Positive Early-Stage Breast Cancer.
abstract: BACKGROUND
  The 21-gene Recurrence Score(®) assay (Oncotype DX(®), Genomic Health, Inc.) is a validated predictor of recurrence risk/chemotherapy benefit in patients with estrogen receptor-positive (ER+) early-stage breast cancer treated with endocrine therapy. The Prosigna(®) assay (NanoString Technologies Inc.) is a validated prognosticator in postmenopausal patients with low-risk ER+ early-stage breast cancer treated with endocrine therapy. The assays were analytically/clinically developed and validated differently. This study focused on comparing recurrence risk estimates as determined by these assays and is the first blinded comparison of these assays on matched patient samples.
  
  
  METHODS
  Sequential breast cancer specimens from postmenopausal, node-negative, ER+ patients treated at the Marin General Hospital were analyzed: first by the 21-gene assay then by the Prosigna assay in an independent lab blinded to the Recurrence Score results.
  
  
  RESULTS
  The final analysis included 52 patients. Correlation between the Recurrence Score and the Prosigna assay results was poor (r = 0.08). Agreement between risk classifications based on these assays was 54%; 4/7 of patients classified as high risk by the Prosigna assay had low Recurrence Score results. Two tumors with high Recurrence Score results had low ER expression (close to positivity threshold); both of which had a low/intermediate Prosigna assay result. The Prosigna assay classified 73.1% and 23.1% of samples as luminal A and luminal B, respectively. A range of Recurrence Score results was observed within the subtypes; 83% of luminal B samples had a low Recurrence Score result.
  
  
  CONCLUSIONS
  Consistent with prior comparisons between the 21-gene and other genomic assays, our study demonstrated substantial differences in the way patients are risk stratified, suggesting that the different assays are not interchangeable.
  
  
  BACKGROUND
  Genomic Health, Inc.
authors.affiliation: University of California, San Francisco, CA, USA. Michael.Alvarado@ucsfmedctr.org.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Alvarado
authors.affiliation: Marin Medical Laboratories, Novato, CA, USA.
authors.forename: Che
authors.initials: C
authors.lastname: Prasad
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Rothney
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Diana B
authors.initials: DB
authors.lastname: Cherbavaz
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Sing
authors.affiliation: University of California, San Francisco, CA, USA.|Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Baehner
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Christer
authors.initials: C
authors.lastname: Svedman
authors.affiliation: Athens University Medical School, Athens, Greece.
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Markopoulos
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology*; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism*; D018570:Risk Assessment
chemical_list: D011960:Receptors, Estrogen
keywords: Adjuvant chemotherapy; Breast cancer; Oncology; Oncotype DX; PAM50; Prosigna, risk assessment; Recurrence Score