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

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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.

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Acknowledgments

We thank Mieke Timmermans, Anita Trapman-Jansen, Vanja de Weerd and Wendy van der Smissen for technical assistance, and Marion Meijer-van Gelder for handling of the clinical data. This study was supported in part by The Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO).

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Authors and Affiliations

  1. Veridex LLC, Johnson & Johnson Company, San Diego, CA, USA

    Yi Zhang, Dmitri Talantov & Yixin Wang

  2. Department of Medical Oncology, Erasmus Medical Center—Josephine Nefkens Institute and Cancer Genomics Centre, Room BE-426, Rotterdam, The Netherlands

    Anieta M. Sieuwerts & John A. Foekens

  3. Department of Cancer Biology, Cancer Clinic Foundation, Cleveland, OH, USA

    Michelle McGreevy

  4. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

    Graham Casey

  5. Institute of Oncology, Ljubljana, Slovenia

    Tanja Cufer & Rastko Golouh

  6. National Cancer Institute, Bari, Italy

    Angelo Paradiso & Francesco Schittulli

  7. Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany

    Nadia Harbeck & Manfred Schmitt

  8. Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Paul N. Span & Fred C. G. J. Sweep

  9. Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA

    David G. Hicks

  10. Department of Breast Services, Cleveland Clinic Foundation, Cleveland, OH, USA

    Joseph Crowe & Joanne Lyons

  11. Department of Molecular Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Raymond R. Tubbs

  12. Department of Solid Tumor Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA

    G. Thomas Budd

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  1. Yi Zhang
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  2. Anieta M. Sieuwerts
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  3. Michelle McGreevy
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  13. Joanne Lyons
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  14. Fred C. G. J. Sweep
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  18. Dmitri Talantov
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  19. Yixin Wang
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Correspondence to John A. Foekens.

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Zhang, Y., Sieuwerts, A.M., McGreevy, M. et al. The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy. Breast Cancer Res Treat 116, 303–309 (2009). https://doi.org/10.1007/s10549-008-0183-2

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  • DOI: https://doi.org/10.1007/s10549-008-0183-2

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