The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy.
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.
Zhang
Yi
Y
Veridex LLC, Johnson & Johnson Company, San Diego, CA, USA.
Sieuwerts
Anieta M
AM
McGreevy
Michelle
M
Casey
Graham
G
Cufer
Tanja
T
Paradiso
Angelo
A
Harbeck
Nadia
N
Span
Paul N
PN
Hicks
David G
DG
Crowe
Joseph
J
Tubbs
Raymond R
RR
Budd
G Thomas
GT
Lyons
Joanne
J
Sweep
Fred C G J
FC
Schmitt
Manfred
M
Schittulli
Francesco
F
Golouh
Rastko
R
Talantov
Dmitri
D
Wang
Yixin
Y
Foekens
John A
JA
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*
D018931:Antineoplastic Agents, Hormonal; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen