Abstract S1-5: Interaction between Goserelin and Tamoxifen in a Controlled Clinical Trial of Adjuvant Endocrine Therapy in Premenopausal Breast Cancer.

Abstract

Abstract Background: Ovarian ablation improves survival in premenopausal women with early breast cancer, but the potential added value by luteinizing hormone-releasing hormone agonists (LHRH-a) to tamoxifen, is still not clear. There has been lack of data reported separately for patients who underwent randomization to both LHRH-a and tamoxifen. Patients and Methods: In Stockholm, 927 patients assigned to the Zoladex in Premenopausal Patients (ZIPP) trial, were included in a 2 x 2 factorial randomization to goserelin (3.6 mg subcutaneously, q 28d), tamoxifen (40 mg daily), the combination of goserelin and tamoxifen or no endocrine therapy for two years, with or without chemo-and/or radiotherapy. The trial was designed to examine the effect of goserelin and the role of interaction between goserelin and tamoxifen in adjuvant therapy of premenopausal breast cancer. We examined as well, the impact of different estrogen receptor (ER) content on treatment effect. The definition of first event was breast cancer recurrence, contra lateral breast cancer or death. The ER content was determined by isoelectric focusing on polyacrylamide gel and receptor values normalized to DNA content. Results: After a median follow up of 12.3 years, goserelin reduced the risk of first event by 32% (p=0.005) in the absence of tamoxifen and tamoxifen reduced the risk by 27% (p=0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (p=0.021) and there was a significant interaction between goserelin and tamoxifen (p=0.025). In highly ER positive tumours, there were 29% fewer events among goserelin treated (p=0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, p=0.007). For tamoxifen, there was not a significant risk reduction at different ER levels, but there was a trend towards interaction between goserelin and tamoxifen effect among the highly ER positive (p=0.076). Discussion: In this strictly randomized cohort of endocrine responsive premenopausal breast cancer, goserelin as well as tamoxifen, reduces the risk of recurrence. However, the combination of goserelin and tamoxifen is not superior to either modality alone. The effect of goserelin seems to be modified by ER levels, whereas tamoxifen effect is not. Women with strongly estrogen receptor positive tumours may benefit more from goserelin treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-5.