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

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.

• Authors: 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
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 116 Issue 2 Pg. 303-9 (Jul 2009) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 18821012 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Selective Estrogen Receptor Modulators
• Tamoxifen

Topics

• Adult
• Aged
• Antineoplastic Agents, Hormonal (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Chemotherapy, Adjuvant
• Female
• Gene Expression
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Staging
• Prognosis
• Risk Factors
• Selective Estrogen Receptor Modulators (therapeutic use)
• Tamoxifen (therapeutic use)