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.

• Authors: International Breast Cancer Study Group (IBCSG), Monica Castiglione-Gertsch, Anne O'Neill, Karen N Price, Aron Goldhirsch, Alan S Coates, Marco Colleoni, M Laura Nasi, Marco Bonetti, Richard D Gelber
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 95 Issue 24 Pg. 1833-46 (Dec 17 2003) ISSN: 1460-2105 [Electronic] United States
• PMID: 14679153 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Hormonal
• Receptors, Estrogen
• Goserelin
• Cyclophosphamide
• Fluorouracil
• Methotrexate

Topics

• Adult
• Amenorrhea (chemically induced)
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology, surgery)
• Chemotherapy, Adjuvant
• Confidence Intervals
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage)
• Goserelin (administration & dosage, adverse effects, therapeutic use)
• Humans
• Incidence
• Lymphatic Metastasis
• Methotrexate (administration & dosage)
• Middle Aged
• Premenopause
• Receptors, Estrogen (metabolism)
• Survival Analysis
• Treatment Outcome