TY - JOUR
T1 - The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy
AU - Zhang, Yi
AU - Sieuwerts, Anieta M.
AU - McGreevy, Michelle
AU - Casey, Graham
AU - Cufer, Tanja
AU - Paradiso, Angelo
AU - Harbeck, Nadia
AU - Span, Paul N.
AU - Hicks, David G.
AU - Crowe, Joseph
AU - Tubbs, Raymond R.
AU - Budd, G. Thomas
AU - Lyons, Joanne
AU - Sweep, Fred C G J
AU - Schmitt, Manfred
AU - Schittulli, Francesco
AU - Golouh, Rastko
AU - Talantov, Dmitri
AU - Wang, Yixin
AU - Foekens, John A.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Gene signature
KW - Prognosis
KW - Tamoxifen benefit
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U2 - 10.1007/s10549-008-0183-2
DO - 10.1007/s10549-008-0183-2
M3 - Article
C2 - 18821012
AN - SCOPUS:67649230285
VL - 116
SP - 303
EP - 309
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -