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 Allred & 2 others C. Kent Osborne, Daniel F. Hayes

Research output: Contribution to journalArticle

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Abstract

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
Volume11
Issue number1
DOIs
StatePublished - Jan 2010

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Estrogen Receptors
Breast Neoplasms
Tamoxifen
Recurrence
Drug Therapy
Genes
Fluorouracil
Doxorubicin
Cyclophosphamide
Anthracyclines
Disease-Free Survival
Survival
National Cancer Institute (U.S.)
Neoplasms
Therapeutics
RNA

ASJC Scopus subject areas

  • Oncology

Cite this

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

In: The Lancet Oncology, Vol. 11, No. 1, 01.2010, p. 55-65.

Research output: Contribution to journalArticle

Albain, KS, Barlow, WE, Shak, S, Hortobagyi, GN, Livingston, RB, Yeh, IT, Ravdin, P, Bugarini, R, Baehner, FL, Davidson, NE, Sledge, GW, Winer, EP, Hudis, C, Ingle, JN, Perez, EA, Pritchard, KI, Shepherd, L, Gralow, JR, Yoshizawa, C, Allred, DC, Osborne, CK & Hayes, DF 2010, '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', The Lancet Oncology, vol. 11, no. 1, pp. 55-65. https://doi.org/10.1016/S1470-2045(09)70314-6
Albain, Kathy S. ; Barlow, William E. ; Shak, Steven ; Hortobagyi, Gabriel N. ; Livingston, Robert B. ; Yeh, I. Tien ; Ravdin, Peter ; Bugarini, Roberto ; Baehner, Frederick L. ; Davidson, Nancy E. ; Sledge, George W. ; Winer, Eric P. ; Hudis, Clifford ; Ingle, James N. ; Perez, Edith A. ; Pritchard, Kathleen I. ; Shepherd, Lois ; Gralow, Julie R. ; Yoshizawa, Carl ; Allred, D. Craig ; Osborne, C. Kent ; Hayes, Daniel F. / 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. In: The Lancet Oncology. 2010 ; Vol. 11, No. 1. pp. 55-65.
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abstract = "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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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.

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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