Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial

Kathy S. Albain, William E. Barlow, Steven Shak, Gabriel N. Hortobagyi, Robert B Livingston, I. Tien Yeh, Peter Ravdin, Roberto Bugarini, Frederick L. Baehner, Nancy E. Davidson, George W. Sledge, Eric P. Winer, Clifford Hudis, James N. Ingle, Edith A. Perez, Kathleen I. Pritchard, Lois Shepherd, Julie R. Gralow, Carl Yoshizawa, D. Craig AllredC. Kent Osborne, Daniel F. Hayes

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Background: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-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.

Original languageEnglish (US)
Pages (from-to)55-65
Number of pages11
JournalThe Lancet Oncology
Issue number1
Publication statusPublished - Jan 2010


ASJC Scopus subject areas

  • Oncology

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