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

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 Veridex LLC
2 Department of Medical Oncology
3 Department of Cancer Biology
4 Department of Preventive Medicine
5 Institute of Oncology
6 National Cancer Institute
7 MRI TUM - Klinikum rechts der Isar
8 Department of Chemical Endocrinology
9 Department of Pathology
10 Department of Breast Services
11 Department of Molecular Pathology
12 Department of Solid Tumor Oncology

To assess the benefit from adjuvant systemic tamoxifen therapy in breast cancer risk groups identified by the previously established prognostic 76-gene signature. 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. In 136 tamoxifen-treated patients, the 76-gene signature identified a group of patients with a poor prognosis [hazard ratio (HR), 4.62;  = 0.0248]. These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR, 0.52;  = 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. 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.

Mots clés: Breast cancer; Gene signature; Prognosis; Tamoxifen benefit

Yi Zhang, Anieta M. Sieuwerts, Michelle Mcgreevy, Graham Casey, Tanja Cufer, et al.. The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy. Breast Cancer Research and Treatment, 2008, 116 (2), pp.303-309. ⟨10.1007/s10549-008-0183-2⟩. ⟨hal-00478265⟩