title: The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy.
abstract: OBJECTIVE
  To assess the benefit from adjuvant systemic tamoxifen therapy in breast cancer risk groups identified by the previously established prognostic 76-gene signature.
  
  
  METHODS
  In 300 lymph node-negative (LNN), estrogen receptor-positive (ER+) breast cancer patients (136 treated with adjuvant tamoxifen, 164 having received no systemic adjuvant therapy), distant metastasis-free survival (DMFS) as a function of the 76-gene signature was determined in a multicenter fashion.
  
  
  RESULTS
  In 136 tamoxifen-treated patients, the 76-gene signature identified a group of patients with a poor prognosis [hazard ratio (HR), 4.62; P = 0.0248]. These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR, 0.52; P = 0.0318) compared with untreated high-risk patients. This represented a 71% increase in relative benefit compared with the 7.2% absolute benefit observed for all 300 patients without using the gene signature. In the low-risk group there was no significant 10-year DMFS benefit of tamoxifen.
  
  
  CONCLUSIONS
  The 76-gene signature defines high-risk patients who benefit from adjuvant tamoxifen therapy. Although we did not study the value of chemotherapy in this study, low-risk patients identified by the 76-gene signature have a prognosis good enough that chemotherapy would be difficult to justify. The prognosis of these patients is sufficiently good, in fact, that a disease-free benefit for tamoxifen therapy is difficult to prove, though benefits in terms of loco-regional relapse and a reduction in risk for contralateral breast cancer might justify hormonal therapy in these patients.
authors.affiliation: Veridex LLC, Johnson & Johnson Company, San Diego, CA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.forename: Michelle
authors.initials: M
authors.lastname: McGreevy
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
authors.forename: Joseph
authors.initials: J
authors.lastname: Crowe
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Budd
authors.forename: Joanne
authors.initials: J
authors.lastname: Lyons
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
authors.forename: Francesco
authors.initials: F
authors.lastname: Schittulli
authors.forename: Rastko
authors.initials: R
authors.lastname: Golouh
authors.forename: Dmitri
authors.initials: D
authors.lastname: Talantov
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen