Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer

Donald A. Berry, Constance Cirrincione, I. Craig Henderson, Marc L. Citron, Daniel R. Budman, Lori J. Goldstein, Silvana Martino, Edith A. Perez, Hyman B. Muss, Larry Norton, Clifford Hudis, Eric P. Winer

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Abstract

Context: Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. Objective: To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. Design, Setting, and Patients: Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. Main Outcome Measures: Disease-free and overall survival. Results: For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. Conclusion: Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.

Original languageEnglish (US)
Pages (from-to)1658-1667
Number of pages10
JournalJournal of the American Medical Association
Volume295
Issue number14
DOIs
StatePublished - Apr 12 2006

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Estrogen Receptors
Breast Neoplasms
Drug Therapy
Doxorubicin
Cyclophosphamide
Paclitaxel
Neoplasms
Adjuvant Chemotherapy
Fluorouracil
Recurrence
Mortality
Tamoxifen
Risk Reduction Behavior
Disease-Free Survival
Leukemia
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Berry, D. A., Cirrincione, C., Henderson, I. C., Citron, M. L., Budman, D. R., Goldstein, L. J., ... Winer, E. P. (2006). Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. Journal of the American Medical Association, 295(14), 1658-1667. https://doi.org/10.1001/jama.295.14.1658

Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. / Berry, Donald A.; Cirrincione, Constance; Henderson, I. Craig; Citron, Marc L.; Budman, Daniel R.; Goldstein, Lori J.; Martino, Silvana; Perez, Edith A.; Muss, Hyman B.; Norton, Larry; Hudis, Clifford; Winer, Eric P.

In: Journal of the American Medical Association, Vol. 295, No. 14, 12.04.2006, p. 1658-1667.

Research output: Contribution to journalArticle

Berry, DA, Cirrincione, C, Henderson, IC, Citron, ML, Budman, DR, Goldstein, LJ, Martino, S, Perez, EA, Muss, HB, Norton, L, Hudis, C & Winer, EP 2006, 'Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer', Journal of the American Medical Association, vol. 295, no. 14, pp. 1658-1667. https://doi.org/10.1001/jama.295.14.1658
Berry, Donald A. ; Cirrincione, Constance ; Henderson, I. Craig ; Citron, Marc L. ; Budman, Daniel R. ; Goldstein, Lori J. ; Martino, Silvana ; Perez, Edith A. ; Muss, Hyman B. ; Norton, Larry ; Hudis, Clifford ; Winer, Eric P. / Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. In: Journal of the American Medical Association. 2006 ; Vol. 295, No. 14. pp. 1658-1667.
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abstract = "Context: Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. Objective: To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. Design, Setting, and Patients: Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. Main Outcome Measures: Disease-free and overall survival. Results: For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21{\%}, 25{\%}, and 23{\%} in the 3 studies, respectively, and 55{\%} comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9{\%}, 12{\%}, and 8{\%} in the 3 studies, and 26{\%} overall. The overall mortality rate reductions associated with chemotherapy improvements were 55{\%} and 23{\%} among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8{\%} more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0{\%} for ER-positive patients; corresponding improvements for overall survival were 16.7{\%} vs 4.0{\%}. Conclusion: Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50{\%} in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.",
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AU - Berry, Donald A.

AU - Cirrincione, Constance

AU - Henderson, I. Craig

AU - Citron, Marc L.

AU - Budman, Daniel R.

AU - Goldstein, Lori J.

AU - Martino, Silvana

AU - Perez, Edith A.

AU - Muss, Hyman B.

AU - Norton, Larry

AU - Hudis, Clifford

AU - Winer, Eric P.

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N2 - Context: Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. Objective: To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. Design, Setting, and Patients: Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. Main Outcome Measures: Disease-free and overall survival. Results: For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. Conclusion: Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.

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