Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer

Joseph A. Sparano, Robert J. Gray, Peter M. Ravdin, Della F. Makower, Kathleen I. Pritchard, Kathy S. Albain, Daniel F. Hayes, Charles E. Geyer, Elizabeth C. Dees, Matthew P. Goetz, John A. Olson, Tracy Lively, Sunil S. Badve, Thomas J. Saphner, Lynne I. Wagner, Timothy J. Whelan, Matthew J. Ellis, Soonmyung Paik, William C. Wood, Maccon M. KeaneHenry L. Gomez Moreno, Pavan S. Reddy, Timothy F. Goggins, Ingrid A. Mayer, Adam M. Brufsky, Deborah L. Toppmeyer, Virginia G. Kaklamani, Jeffrey L. Berenberg, Jeffrey Abrams, George W. Sledge

Research output: Contribution to journalArticle

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Abstract

The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.

Original languageEnglish (US)
Pages (from-to)2395-2405
Number of pages11
JournalNew England Journal of Medicine
Volume380
Issue number25
DOIs
StatePublished - Jun 20 2019

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Breast Neoplasms
Recurrence
Therapeutics
Drug Therapy
Confidence Intervals
Genes
Tamoxifen
Adjuvant Chemotherapy
Proportional Hazards Models
Age Groups
Hormones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. / Sparano, Joseph A.; Gray, Robert J.; Ravdin, Peter M.; Makower, Della F.; Pritchard, Kathleen I.; Albain, Kathy S.; Hayes, Daniel F.; Geyer, Charles E.; Dees, Elizabeth C.; Goetz, Matthew P.; Olson, John A.; Lively, Tracy; Badve, Sunil S.; Saphner, Thomas J.; Wagner, Lynne I.; Whelan, Timothy J.; Ellis, Matthew J.; Paik, Soonmyung; Wood, William C.; Keane, Maccon M.; Gomez Moreno, Henry L.; Reddy, Pavan S.; Goggins, Timothy F.; Mayer, Ingrid A.; Brufsky, Adam M.; Toppmeyer, Deborah L.; Kaklamani, Virginia G.; Berenberg, Jeffrey L.; Abrams, Jeffrey; Sledge, George W.

In: New England Journal of Medicine, Vol. 380, No. 25, 20.06.2019, p. 2395-2405.

Research output: Contribution to journalArticle

Sparano, JA, Gray, RJ, Ravdin, PM, Makower, DF, Pritchard, KI, Albain, KS, Hayes, DF, Geyer, CE, Dees, EC, Goetz, MP, Olson, JA, Lively, T, Badve, SS, Saphner, TJ, Wagner, LI, Whelan, TJ, Ellis, MJ, Paik, S, Wood, WC, Keane, MM, Gomez Moreno, HL, Reddy, PS, Goggins, TF, Mayer, IA, Brufsky, AM, Toppmeyer, DL, Kaklamani, VG, Berenberg, JL, Abrams, J & Sledge, GW 2019, 'Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer', New England Journal of Medicine, vol. 380, no. 25, pp. 2395-2405. https://doi.org/10.1056/NEJMoa1904819
Sparano, Joseph A. ; Gray, Robert J. ; Ravdin, Peter M. ; Makower, Della F. ; Pritchard, Kathleen I. ; Albain, Kathy S. ; Hayes, Daniel F. ; Geyer, Charles E. ; Dees, Elizabeth C. ; Goetz, Matthew P. ; Olson, John A. ; Lively, Tracy ; Badve, Sunil S. ; Saphner, Thomas J. ; Wagner, Lynne I. ; Whelan, Timothy J. ; Ellis, Matthew J. ; Paik, Soonmyung ; Wood, William C. ; Keane, Maccon M. ; Gomez Moreno, Henry L. ; Reddy, Pavan S. ; Goggins, Timothy F. ; Mayer, Ingrid A. ; Brufsky, Adam M. ; Toppmeyer, Deborah L. ; Kaklamani, Virginia G. ; Berenberg, Jeffrey L. ; Abrams, Jeffrey ; Sledge, George W. / Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 25. pp. 2395-2405.
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abstract = "The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95{\%} confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95{\%} CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95{\%} CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5{\%} (≤1.8±0.9{\%}) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0{\%} with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10{\%} among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4{\%}) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3{\%}). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.",
author = "Sparano, {Joseph A.} and Gray, {Robert J.} and Ravdin, {Peter M.} and Makower, {Della F.} and Pritchard, {Kathleen I.} and Albain, {Kathy S.} and Hayes, {Daniel F.} and Geyer, {Charles E.} and Dees, {Elizabeth C.} and Goetz, {Matthew P.} and Olson, {John A.} and Tracy Lively and Badve, {Sunil S.} and Saphner, {Thomas J.} and Wagner, {Lynne I.} and Whelan, {Timothy J.} and Ellis, {Matthew J.} and Soonmyung Paik and Wood, {William C.} and Keane, {Maccon M.} and {Gomez Moreno}, {Henry L.} and Reddy, {Pavan S.} and Goggins, {Timothy F.} and Mayer, {Ingrid A.} and Brufsky, {Adam M.} and Toppmeyer, {Deborah L.} and Kaklamani, {Virginia G.} and Berenberg, {Jeffrey L.} and Jeffrey Abrams and Sledge, {George W.}",
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TY - JOUR

T1 - Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer

AU - Sparano, Joseph A.

AU - Gray, Robert J.

AU - Ravdin, Peter M.

AU - Makower, Della F.

AU - Pritchard, Kathleen I.

AU - Albain, Kathy S.

AU - Hayes, Daniel F.

AU - Geyer, Charles E.

AU - Dees, Elizabeth C.

AU - Goetz, Matthew P.

AU - Olson, John A.

AU - Lively, Tracy

AU - Badve, Sunil S.

AU - Saphner, Thomas J.

AU - Wagner, Lynne I.

AU - Whelan, Timothy J.

AU - Ellis, Matthew J.

AU - Paik, Soonmyung

AU - Wood, William C.

AU - Keane, Maccon M.

AU - Gomez Moreno, Henry L.

AU - Reddy, Pavan S.

AU - Goggins, Timothy F.

AU - Mayer, Ingrid A.

AU - Brufsky, Adam M.

AU - Toppmeyer, Deborah L.

AU - Kaklamani, Virginia G.

AU - Berenberg, Jeffrey L.

AU - Abrams, Jeffrey

AU - Sledge, George W.

PY - 2019/6/20

Y1 - 2019/6/20

N2 - The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.

AB - The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.

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