Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: A randomized trial

Monica Castiglione-Gertsch, Anne O'Neill, Karen N. Price, Aron Goldhirsch, Alan S. Coates, Marco Colleoni, M. Laura Nasi, Marco Bonetti, Richard D. Gelber

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Abstract

Background: Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone. Methods: From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF → goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS). Results: Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF → goserelin = 88%, 95% CI = 82% to 94%) than if they received goserelin alone (5-year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women. Conclusions: Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied.

Original languageEnglish
Pages (from-to)1833-1846
Number of pages14
JournalJournal of the National Cancer Institute
Volume95
Issue number24
Publication statusPublished - Dec 17 2003

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Goserelin
Adjuvant Chemotherapy
Estrogen Receptors
Disease-Free Survival
Lymph Nodes
Methotrexate
Fluorouracil
Cyclophosphamide
Breast Neoplasms
Confidence Intervals
Drug Therapy
Endocrine System Diseases
Therapeutics
Combination Drug Therapy
Gonadotropin-Releasing Hormone
Neoplasms
Radiotherapy
Randomized Controlled Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer : A randomized trial. / Castiglione-Gertsch, Monica; O'Neill, Anne; Price, Karen N.; Goldhirsch, Aron; Coates, Alan S.; Colleoni, Marco; Nasi, M. Laura; Bonetti, Marco; Gelber, Richard D.

In: Journal of the National Cancer Institute, Vol. 95, No. 24, 17.12.2003, p. 1833-1846.

Research output: Contribution to journalArticle

Castiglione-Gertsch, Monica ; O'Neill, Anne ; Price, Karen N. ; Goldhirsch, Aron ; Coates, Alan S. ; Colleoni, Marco ; Nasi, M. Laura ; Bonetti, Marco ; Gelber, Richard D. / Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer : A randomized trial. In: Journal of the National Cancer Institute. 2003 ; Vol. 95, No. 24. pp. 1833-1846.
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title = "Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: A randomized trial",
abstract = "Background: Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone. Methods: From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of {"}classical{"} CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF → goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30{\%}), ER-positive (68{\%}), or ER status unknown (3{\%}). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS). Results: Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84{\%}, 95{\%} confidence interval [CI] = 77{\%} to 91{\%}; 5-year DFS for CMF → goserelin = 88{\%}, 95{\%} CI = 82{\%} to 94{\%}) than if they received goserelin alone (5-year DFS = 73{\%}, 95{\%} CI = 64{\%} to 81{\%}). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81{\%}, 95{\%} CI = 76{\%} to 87{\%}), whereas sequential therapy (5-year DFS = 86{\%}, 95{\%} CI = 82{\%} to 91{\%}) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women. Conclusions: Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied.",
author = "Monica Castiglione-Gertsch and Anne O'Neill and Price, {Karen N.} and Aron Goldhirsch and Coates, {Alan S.} and Marco Colleoni and Nasi, {M. Laura} and Marco Bonetti and Gelber, {Richard D.}",
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T1 - Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer

T2 - A randomized trial

AU - Castiglione-Gertsch, Monica

AU - O'Neill, Anne

AU - Price, Karen N.

AU - Goldhirsch, Aron

AU - Coates, Alan S.

AU - Colleoni, Marco

AU - Nasi, M. Laura

AU - Bonetti, Marco

AU - Gelber, Richard D.

PY - 2003/12/17

Y1 - 2003/12/17

N2 - Background: Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone. Methods: From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF → goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS). Results: Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF → goserelin = 88%, 95% CI = 82% to 94%) than if they received goserelin alone (5-year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women. Conclusions: Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied.

AB - Background: Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone. Methods: From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF → goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS). Results: Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF → goserelin = 88%, 95% CI = 82% to 94%) than if they received goserelin alone (5-year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women. Conclusions: Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied.

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