Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in Postmenopausal Women With Node-Positive, Oestrogen-Receptor-Positive Breast Cancer on Chemotherapy
Lancet Oncol. 2010 Jan 1;11(1):55-65, KS Albain, WE Barlow, S Shak, GN Hortobagyi, RB Livingston, I-T Yeh, P Ravdin, R Bugarini, FL Baehner, NE Davidson, GW Sledge, EP Winer, C Hudis, JN Ingle, EA Perez, KI Pritchard, L Shepherd, JR Gralow, C Yoshizawa, DC Allred, CK Osborne, DF Hayes, for The Breast Cancer Intergroup of North America
ABSTRACT
Background: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogenreceptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence.
Methods: The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes.
Findings: There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0•006; hazard ratio [HR] 2•64, 95% CI 1•33–5•27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0•97; HR 1•02, 0•54–1•93), but an improvement in disease-free survival for those with a high recurrence score (score ≥31; log-rank p=0•033; HR 0•59, 0•35–1•01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0•029), with no additional prediction beyond 5 years (p=0•58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival.
Interpretation: The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes.
Funding: National Cancer Institute and Genomic Health.
