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Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Therapy in Premenopausal Patients With Node-Positive Breast Cancer: The Zoladex Early Breast Cancer Research Association Study

From the Klinik fur Gynakologie und Gerburtshilfe, Kiel, Universitatsklinik Frauenklinik, Frankfurt, Institute fur Medizinische Biometrie und Informatik and University Hospital, Freiburg, Frauenklinik vom Roten Kreuz, Munich, Universitätsklinikum Heidelberg, Heidelberg, and Universitätskrankenhaus Eppendorf, Hamburg, Germany; Nottingham City Hospital, Nottingham, Imperial Cancer Research Fund, Guy’s and St Thomas’ Hospital, London, Christie Hospital, Manchester, and AstraZeneca, Macclesfield, United Kingdom; Medicin Chef de Service du Centre-Antoine, Nice, France; University Hospital AMC, Amsterdam, the Netherlands; Istituto Nazionale Tumori, Naples, Italy; and National Institute of Oncology, Budapest, Hungary.

Address reprint requests to Walter Jonat, PhD, Klinik fur Gynakologie und Gerburtshilfe, University of Kiel, D-24105 Kiel, Germany; email: jonat{at}email.uni-kiel.de

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause.

PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer.

RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P = .0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group.

CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

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