Adjuvant chemotherapy guided by 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, M. P. Goetz, J. A. Olson, T. Lively, Sunil Badve, T. J. Saphner, L. I. Wagner, T. J. Whelan, M. J. Ellis, S. Paik, W. C. Wood, P. M. Ravdin, M. M. KeaneH. L. Gomez Moreno, P. S. Reddy, T. F. Goggins, I. A. Mayer, A. M. Brufsky, D. L. Toppmeyer, V. G. Kaklamani, J. L. Berenberg, J. Abrams, G. W. Sledge

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P = 0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P = 0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalNew England Journal of Medicine
Volume379
Issue number2
DOIs
StatePublished - Jul 12 2018

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Adjuvant Chemotherapy
Breast Neoplasms
Gene Expression
Recurrence
Drug Therapy
Disease-Free Survival
Therapeutics
Second Primary Neoplasms
Group Psychotherapy
Hormones
Genes
Uncertainty
Confidence Intervals
Survival

ASJC Scopus subject areas

  • Medicine(all)

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Sparano, J. A., Gray, R. J., Makower, D. F., Pritchard, K. I., Albain, K. S., Hayes, D. F., ... Sledge, G. W. (2018). Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. New England Journal of Medicine, 379(2), 111-121. https://doi.org/10.1056/NEJMoa1804710

Adjuvant chemotherapy guided by 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.; Goetz, M. P.; Olson, J. A.; Lively, T.; Badve, Sunil; Saphner, T. J.; Wagner, L. I.; Whelan, T. J.; Ellis, M. J.; Paik, S.; Wood, W. C.; Ravdin, P. M.; 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.; Berenberg, J. L.; Abrams, J.; Sledge, G. W.

In: New England Journal of Medicine, Vol. 379, No. 2, 12.07.2018, p. 111-121.

Research output: Contribution to journalArticle

Sparano, JA, Gray, RJ, Makower, DF, Pritchard, KI, Albain, KS, Hayes, DF, Geyer, CE, Dees, EC, Goetz, MP, Olson, JA, Lively, T, Badve, S, Saphner, TJ, Wagner, LI, Whelan, TJ, Ellis, MJ, Paik, S, Wood, WC, Ravdin, PM, Keane, MM, Gomez Moreno, HL, Reddy, PS, Goggins, TF, Mayer, IA, Brufsky, AM, Toppmeyer, DL, Kaklamani, VG, Berenberg, JL, Abrams, J & Sledge, GW 2018, 'Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer', New England Journal of Medicine, vol. 379, no. 2, pp. 111-121. https://doi.org/10.1056/NEJMoa1804710
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. New England Journal of Medicine. 2018 Jul 12;379(2):111-121. https://doi.org/10.1056/NEJMoa1804710
Sparano, J. A. ; Gray, R. J. ; Makower, D. F. ; Pritchard, K. I. ; Albain, K. S. ; Hayes, D. F. ; Geyer, C. E. ; Dees, E. C. ; Goetz, M. P. ; Olson, J. A. ; Lively, T. ; Badve, Sunil ; Saphner, T. J. ; Wagner, L. I. ; Whelan, T. J. ; Ellis, M. J. ; Paik, S. ; Wood, W. C. ; Ravdin, P. M. ; 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. ; Berenberg, J. L. ; Abrams, J. ; Sledge, G. W. / Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 2. pp. 111-121.
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abstract = "BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69{\%}) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95{\%} confidence interval, 0.94 to 1.24; P = 0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3{\%} in the endocrine-therapy group and 84.3{\%} in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5{\%} and 95.0{\%}) or at a distant or local-regional site (92.2{\%} and 92.9{\%}), and overall survival (93.9{\%} and 93.8{\%}). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P = 0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger.",
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 Goetz, {M. P.} and Olson, {J. A.} and T. Lively and Sunil Badve and Saphner, {T. J.} and Wagner, {L. I.} and Whelan, {T. J.} and Ellis, {M. J.} and S. Paik and Wood, {W. C.} and Ravdin, {P. M.} 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 Berenberg, {J. L.} and J. Abrams and Sledge, {G. W.}",
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TY - JOUR

T1 - Adjuvant chemotherapy guided by 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 - Goetz, M. P.

AU - Olson, J. A.

AU - Lively, T.

AU - Badve, Sunil

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. M.

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 - Berenberg, J. L.

AU - Abrams, J.

AU - Sledge, G. W.

PY - 2018/7/12

Y1 - 2018/7/12

N2 - BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P = 0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P = 0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger.

AB - BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P = 0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P = 0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger.

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