Long-term Effectiveness of Adjuvant Goserelin in Premenopausal Women With Early Breast Cancer

Abstract

BackgroundSystematic reviews have found that luteinizing hormone–releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.MethodsWe 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.ResultsFifteen 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.ConclusionsTwo 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.

Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer

“…Furthermore, the single laboratory analyses of ER content with a quantitative cytosol method, allowed an analysis of the effect of different receptor levels on outcome. This formal test of interaction between goserelin and tamoxifen in a randomised cohort confirms the indication made in the Hackshaw report, that tamoxifen provides no additional benefit among women treated with goserelin [10]. The same is true for the opposite, where goserelin provides no additional benefit for tamoxifen treated.…”

“…randomisation to tamoxifen had been optional in some centres [9,10]. Subsequently, some women received tamoxifen electively.…”

“…At a median follow-up of 12 years, two years treatment with goserelin was as effective as two years of tamoxifen. In those not treated with tamoxifen, there was a large survival and recurrence benefit with goserelin (13.9% fewer events, 95% confidence interval (CI), -19.4 to -7.5), and the addition of tamoxifen to goserelin showed marginal but not statistically significant improvement (2.8% fewer events, CI -7.7 to 2.0) [10]. One of the limitations of the ZIPP trial is that randomisation was not strict factorial at all participating study sites.…”

“…Results from the ZIPP trial have been reported and are recently updated [9,10]. At a median follow-up of 12 years, two years treatment with goserelin was as effective as two years of tamoxifen.…”

Adjuvant Endocrine Therapy for Early Breast Cancer: A Systematic Review of the Evidence for the 2014 Cancer Care Ontario Systemic Therapy Guideline

“…The ZIPP Study 121,122 : The zipp study included patients less than 50 years of age with invasive, operable breast cancer in one breast and no signs of metastasis. The study description and some results were included in the other systematic reviews and metaanalyses.…”