Prospective validation of a 21-gene expression assay in breast cancer

J. A. Sparano, R. J. Gray, D. F. Makower, K. I. Pritchard, K. S. Albain, D. F. Hayes, C. E. Geyer, E. C. Dees, E. A. Perez, J. A. Olson, J. A. Zujewski, T. Lively, S. S. Badve, T. J. Saphner, L. I. Wagner, T. J. Whelan, M. J. Ellis, S. Paik, W. C. Wood, P. RavdinM. M. Keane, H. L. Gomez Moreno, P. S. Reddy, T. F. Goggins, I. A. Mayer, A. M. Brufsky, D. L. Toppmeyer, V. G. Kaklamani, J. N. Atkins, J. L. Berenberg, G. W. Sledge

Research output: Contribution to journalArticle

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Abstract

Background Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. Methods We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). Results Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). Conclusions Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone.

Original languageEnglish (US)
Pages (from-to)2005-2014
Number of pages10
JournalNew England Journal of Medicine
Volume373
Issue number21
DOIs
StatePublished - Nov 19 2015

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Breast Neoplasms
Gene Expression
Recurrence
Confidence Intervals
Neoplasms
Adjuvant Chemotherapy
Hormones
Guidelines
Drug Therapy
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome
Paraffin
Population
Disease-Free Survival
Therapeutics
Survival Rate
Biomarkers
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sparano, J. A., Gray, R. J., Makower, D. F., Pritchard, K. I., Albain, K. S., Hayes, D. F., ... Sledge, G. W. (2015). Prospective validation of a 21-gene expression assay in breast cancer. New England Journal of Medicine, 373(21), 2005-2014. https://doi.org/10.1056/NEJMoa1510764

Prospective validation of a 21-gene expression assay in breast cancer. / Sparano, J. A.; Gray, R. J.; Makower, D. F.; Pritchard, K. I.; Albain, K. S.; Hayes, D. F.; Geyer, C. E.; Dees, E. C.; Perez, E. A.; Olson, J. A.; Zujewski, J. A.; Lively, T.; Badve, S. S.; Saphner, T. J.; Wagner, L. I.; Whelan, T. J.; Ellis, M. J.; Paik, S.; Wood, W. C.; Ravdin, P.; Keane, M. M.; Gomez Moreno, H. L.; Reddy, P. S.; Goggins, T. F.; Mayer, I. A.; Brufsky, A. M.; Toppmeyer, D. L.; Kaklamani, V. G.; Atkins, J. N.; Berenberg, J. L.; Sledge, G. W.

In: New England Journal of Medicine, Vol. 373, No. 21, 19.11.2015, p. 2005-2014.

Research output: Contribution to journalArticle

Sparano, JA, Gray, RJ, Makower, DF, Pritchard, KI, Albain, KS, Hayes, DF, Geyer, CE, Dees, EC, Perez, EA, Olson, JA, Zujewski, JA, Lively, T, Badve, SS, Saphner, TJ, Wagner, LI, Whelan, TJ, Ellis, MJ, Paik, S, Wood, WC, Ravdin, P, Keane, MM, Gomez Moreno, HL, Reddy, PS, Goggins, TF, Mayer, IA, Brufsky, AM, Toppmeyer, DL, Kaklamani, VG, Atkins, JN, Berenberg, JL & Sledge, GW 2015, 'Prospective validation of a 21-gene expression assay in breast cancer', New England Journal of Medicine, vol. 373, no. 21, pp. 2005-2014. https://doi.org/10.1056/NEJMoa1510764
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF et al. Prospective validation of a 21-gene expression assay in breast cancer. New England Journal of Medicine. 2015 Nov 19;373(21):2005-2014. https://doi.org/10.1056/NEJMoa1510764
Sparano, J. A. ; Gray, R. J. ; Makower, D. F. ; Pritchard, K. I. ; Albain, K. S. ; Hayes, D. F. ; Geyer, C. E. ; Dees, E. C. ; Perez, E. A. ; Olson, J. A. ; Zujewski, J. A. ; Lively, T. ; Badve, S. S. ; Saphner, T. J. ; Wagner, L. I. ; Whelan, T. J. ; Ellis, M. J. ; Paik, S. ; Wood, W. C. ; Ravdin, P. ; Keane, M. M. ; Gomez Moreno, H. L. ; Reddy, P. S. ; Goggins, T. F. ; Mayer, I. A. ; Brufsky, A. M. ; Toppmeyer, D. L. ; Kaklamani, V. G. ; Atkins, J. N. ; Berenberg, J. L. ; Sledge, G. W. / Prospective validation of a 21-gene expression assay in breast cancer. In: New England Journal of Medicine. 2015 ; Vol. 373, No. 21. pp. 2005-2014.
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abstract = "Background Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. Methods We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). Results Of the 10,253 eligible women enrolled, 1626 women (15.9{\%}) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8{\%} (95{\%} confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3{\%} (95{\%} CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7{\%} (95{\%} CI, 97.9 to 99.2), and the rate of overall survival was 98.0{\%} (95{\%} CI, 97.1 to 98.6). Conclusions Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone.",
author = "Sparano, {J. A.} and Gray, {R. J.} and Makower, {D. F.} and Pritchard, {K. I.} and Albain, {K. S.} and Hayes, {D. F.} and Geyer, {C. E.} and Dees, {E. C.} and Perez, {E. A.} and Olson, {J. A.} and Zujewski, {J. A.} and T. Lively and Badve, {S. S.} and Saphner, {T. J.} and Wagner, {L. I.} and Whelan, {T. J.} and Ellis, {M. J.} and S. Paik and Wood, {W. C.} and P. Ravdin and Keane, {M. M.} and {Gomez Moreno}, {H. L.} and Reddy, {P. S.} and Goggins, {T. F.} and Mayer, {I. A.} and Brufsky, {A. M.} and Toppmeyer, {D. L.} and Kaklamani, {V. G.} and Atkins, {J. N.} and Berenberg, {J. L.} and Sledge, {G. W.}",
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TY - JOUR

T1 - Prospective validation of a 21-gene expression assay in breast cancer

AU - Sparano, J. A.

AU - Gray, R. J.

AU - Makower, D. F.

AU - Pritchard, K. I.

AU - Albain, K. S.

AU - Hayes, D. F.

AU - Geyer, C. E.

AU - Dees, E. C.

AU - Perez, E. A.

AU - Olson, J. A.

AU - Zujewski, J. A.

AU - Lively, T.

AU - Badve, S. S.

AU - Saphner, T. J.

AU - Wagner, L. I.

AU - Whelan, T. J.

AU - Ellis, M. J.

AU - Paik, S.

AU - Wood, W. C.

AU - Ravdin, P.

AU - Keane, M. M.

AU - Gomez Moreno, H. L.

AU - Reddy, P. S.

AU - Goggins, T. F.

AU - Mayer, I. A.

AU - Brufsky, A. M.

AU - Toppmeyer, D. L.

AU - Kaklamani, V. G.

AU - Atkins, J. N.

AU - Berenberg, J. L.

AU - Sledge, G. W.

PY - 2015/11/19

Y1 - 2015/11/19

N2 - Background Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. Methods We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). Results Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). Conclusions Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone.

AB - Background Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. Methods We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). Results Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). Conclusions Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone.

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JO - New England Journal of Medicine

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