Breast Cancer Research and Treatment

, Volume 116, Issue 2, pp 303–309

The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy

  • Yi Zhang
  • Anieta M. Sieuwerts
  • Michelle McGreevy
  • Graham Casey
  • Tanja Cufer
  • Angelo Paradiso
  • Nadia Harbeck
  • Paul N. Span
  • David G. Hicks
  • Joseph Crowe
  • Raymond R. Tubbs
  • G. Thomas Budd
  • Joanne Lyons
  • Fred C. G. J. Sweep
  • Manfred Schmitt
  • Francesco Schittulli
  • Rastko Golouh
  • Dmitri Talantov
  • Yixin Wang
  • John A. Foekens
Clinical Trial

DOI: 10.1007/s10549-008-0183-2

Cite this article as:
Zhang, Y., Sieuwerts, A.M., McGreevy, M. et al. Breast Cancer Res Treat (2009) 116: 303. doi:10.1007/s10549-008-0183-2

Abstract

Purpose 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.

Keywords

Breast cancerGene signaturePrognosisTamoxifen benefit

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Yi Zhang
    • 1
  • Anieta M. Sieuwerts
    • 2
  • Michelle McGreevy
    • 3
  • Graham Casey
    • 4
  • Tanja Cufer
    • 5
  • Angelo Paradiso
    • 6
  • Nadia Harbeck
    • 7
  • Paul N. Span
    • 8
  • David G. Hicks
    • 9
  • Joseph Crowe
    • 10
  • Raymond R. Tubbs
    • 11
  • G. Thomas Budd
    • 12
  • Joanne Lyons
    • 10
  • Fred C. G. J. Sweep
    • 8
  • Manfred Schmitt
    • 7
  • Francesco Schittulli
    • 6
  • Rastko Golouh
    • 5
  • Dmitri Talantov
    • 1
  • Yixin Wang
    • 1
  • John A. Foekens
    • 2
  1. 1.Veridex LLCJohnson & Johnson CompanySan DiegoUSA
  2. 2.Department of Medical OncologyErasmus Medical Center—Josephine Nefkens Institute and Cancer Genomics CentreRotterdamThe Netherlands
  3. 3.Department of Cancer BiologyCancer Clinic FoundationClevelandUSA
  4. 4.Department of Preventive MedicineUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Institute of OncologyLjubljanaSlovenia
  6. 6.National Cancer InstituteBariItaly
  7. 7.Department of Obstetrics and Gynecology, Klinikum rechts der IsarTechnische Universitaet MuenchenMunichGermany
  8. 8.Department of Chemical EndocrinologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  9. 9.Department of PathologyUniversity of Rochester Medical CenterRochesterUSA
  10. 10.Department of Breast ServicesCleveland Clinic FoundationClevelandUSA
  11. 11.Department of Molecular PathologyCleveland Clinic FoundationClevelandUSA
  12. 12.Department of Solid Tumor OncologyCleveland Clinic FoundationClevelandUSA