Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and leukemia group B 40101

Lawrence N. Shulman, Constance T. Cirrincione, Donald A. Berry, Heather P. Becker, Edith A. Perez, Ruth O'Regan, Silvana Martino, James N. Atkins, Erica Mayer, Charles J. Schneider, Gretchen Kimmick, Larry Norton, Hyman Muss, Eric P. Winer, Clifford Hudis

Research output: Contribution to journalArticle

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Abstract

Purpose: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/ cyclophosphamide (AC), but with reduced toxicity. Patients and Methods: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). Results: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. Conclusion: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.

Original languageEnglish (US)
Pages (from-to)4071-4076
Number of pages6
JournalJournal of Clinical Oncology
Volume30
Issue number33
DOIs
StatePublished - Nov 20 2012

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Adjuvant Chemotherapy
Paclitaxel
Doxorubicin
Cyclophosphamide
Leukemia
Breast Neoplasms
Recurrence
Survival
Progesterone Receptors
Drug Therapy
Estrogen Receptors
Neoplasms
Therapeutics
human ERBB2 protein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes : Cancer and leukemia group B 40101. / Shulman, Lawrence N.; Cirrincione, Constance T.; Berry, Donald A.; Becker, Heather P.; Perez, Edith A.; O'Regan, Ruth; Martino, Silvana; Atkins, James N.; Mayer, Erica; Schneider, Charles J.; Kimmick, Gretchen; Norton, Larry; Muss, Hyman; Winer, Eric P.; Hudis, Clifford.

In: Journal of Clinical Oncology, Vol. 30, No. 33, 20.11.2012, p. 4071-4076.

Research output: Contribution to journalArticle

Shulman, LN, Cirrincione, CT, Berry, DA, Becker, HP, Perez, EA, O'Regan, R, Martino, S, Atkins, JN, Mayer, E, Schneider, CJ, Kimmick, G, Norton, L, Muss, H, Winer, EP & Hudis, C 2012, 'Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and leukemia group B 40101', Journal of Clinical Oncology, vol. 30, no. 33, pp. 4071-4076. https://doi.org/10.1200/JCO.2011.40.6405
Shulman, Lawrence N. ; Cirrincione, Constance T. ; Berry, Donald A. ; Becker, Heather P. ; Perez, Edith A. ; O'Regan, Ruth ; Martino, Silvana ; Atkins, James N. ; Mayer, Erica ; Schneider, Charles J. ; Kimmick, Gretchen ; Norton, Larry ; Muss, Hyman ; Winer, Eric P. ; Hudis, Clifford. / Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes : Cancer and leukemia group B 40101. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 33. pp. 4071-4076.
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title = "Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and leukemia group B 40101",
abstract = "Purpose: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/ cyclophosphamide (AC), but with reduced toxicity. Patients and Methods: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). Results: A total of 3,171 patients were enrolled; 94{\%} were node-negative and 6{\%} had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9{\%} and 91.8{\%} for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95{\%} CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3{\%} and 96.3{\%} for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95{\%} CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. Conclusion: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.",
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T1 - Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes

T2 - Cancer and leukemia group B 40101

AU - Shulman, Lawrence N.

AU - Cirrincione, Constance T.

AU - Berry, Donald A.

AU - Becker, Heather P.

AU - Perez, Edith A.

AU - O'Regan, Ruth

AU - Martino, Silvana

AU - Atkins, James N.

AU - Mayer, Erica

AU - Schneider, Charles J.

AU - Kimmick, Gretchen

AU - Norton, Larry

AU - Muss, Hyman

AU - Winer, Eric P.

AU - Hudis, Clifford

PY - 2012/11/20

Y1 - 2012/11/20

N2 - Purpose: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/ cyclophosphamide (AC), but with reduced toxicity. Patients and Methods: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). Results: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. Conclusion: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.

AB - Purpose: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/ cyclophosphamide (AC), but with reduced toxicity. Patients and Methods: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). Results: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. Conclusion: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.

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