TY - JOUR
T1 - Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy
T2 - a retrospective analysis of a randomised trial
AU - Albain, Kathy S.
AU - Barlow, William E.
AU - Shak, Steven
AU - Hortobagyi, Gabriel N.
AU - Livingston, Robert B.
AU - Yeh, I. Tien
AU - Ravdin, Peter
AU - Bugarini, Roberto
AU - Baehner, Frederick L.
AU - Davidson, Nancy E.
AU - Sledge, George W.
AU - Winer, Eric P.
AU - Hudis, Clifford
AU - Ingle, James N.
AU - Perez, Edith A.
AU - Pritchard, Kathleen I.
AU - Shepherd, Lois
AU - Gralow, Julie R.
AU - Yoshizawa, Carl
AU - Allred, D. Craig
AU - Osborne, C. Kent
AU - Hayes, Daniel F.
N1 - Funding Information:
KSA, RBL, and PR declared occasional speaker's bureau, continuing medical education lecture, or advisory board honoraria for Genomic Health. KSA, WEB, and DFH declared research funding from Genomic Health to their institutions but with no direct payments to themselves. GWS and DCA have served as paid consultants to Genomic Health. DFH has collaborated with Genomic Health on other unfunded research endeavours. PR has ownership interest in Adjuvant Online. CH had equity interest in Genomic Health until June, 2008, when it was divested 100%. SS, RB, FLB, and CY are full-time employees and stockholders in Genomic Health. GNH, I-TY, NED, EPW, JNI, EAP, KIP, LS, JRG, and CKO declared that they have no relevant conflicts of interest.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1470-2045(09)70314-6
DO - 10.1016/S1470-2045(09)70314-6
M3 - Article
C2 - 20005174
AN - SCOPUS:73249140371
SN - 1470-2045
VL - 11
SP - 55
EP - 65
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 1
ER -