Journal of the National Cancer Institute Advance Access originally published online on February 24, 2009
JNCI Journal of the National Cancer Institute 2009 101(5):341-349; doi:10.1093/jnci/djn498
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Long-term Effectiveness of Adjuvant Goserelin in Premenopausal Women With Early Breast Cancer
Affiliations of authors: Cancer Research UK & UCL Cancer Trials Centre (AH, KM, SF, KR) and Department of Surgery (MB, RS), University College London, London, UK; Stockholm Breast Cancer Study Group, Stockholm, Sweden (TF, UJ); SE Sweden Breast Cancer Group, Linköping, Sweden (BN, HF); Gruppo Interdisciplinare Valutazione Interventi in Oncologia, S. Maria Imbaro., Italy (AN, MV)
Correspondence to: Allan Hackshaw, M.Sc., Cancer Research UK & UCL Cancer Trials Centre, University College London, 90 Tottenham Court Rd, London W1T 4TJ, UK (e-mail: ah{at}ctc.ucl.ac.uk).
Background: Systematic reviews have found that luteinizing hormone–releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.
Methods: We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen.
Results: Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelin compared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant.
Conclusions: Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when goserelin was added.
| Context and Caveats Prior knowledge Ovarian suppression by treatment with goserelin had been shown to reduce the risk of mortality in premenopausal breast cancer patients, but data on the long-term benefit of this treatment were lacking. Study design The analysis was based on a randomized trial with 2 x 2 factorial assignment of breast cancer patients younger than 50 years to no hormonal therapy or 2 years of treatment with tamoxifen alone, goserelin alone, or goserelin plus tamoxifen. Kaplan–Meier curves were constructed and hazard ratios and absolute risk reductions were calculated to compare treatment groups in terms of survival and recurrence outcomes. Contribution This study quantified the absolute risk reduction of mortality and recurrence conferred by goserelin treatment among women who did and did not take tamoxifen based on long-term follow-up (mean follow-up time = 11 years). Implications For every 100 women younger than 50 years and not treated with tamoxifen, 2 years of goserelin treatment would result in 8.5 fewer breast cancer deaths compared to those not given goserelin. The benefit of goserelin treatment in women treated with tamoxifen, if any, would be smaller (possibly 2.6 fewer deaths). Limitations Women in the trial were treated with tamoxifen for 2 years, which is currently not standard practice. The trial did not address the question of the optimal frequency and duration of goserelin treatment. From the Editors
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Manuscript received June 3, 2008; revised November 17, 2008; accepted December 12, 2008.
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J Natl Cancer Inst 2009 101: 281.
J Natl Cancer Inst 2009 101: 281.
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  Adjuvant Goserelin for Early-Stage Breast Cancer Journal Watch Oncology and Hematology, March 24, 2009; 2009(324): 2 - 2. [Full Text]
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