As reported in the Journal of Clinical Oncology by Johansson et al, 20-year follow-up of the Stockholm trial (STO-5) has shown long-term reduction in the risk of distant recurrence with 2 years of adjuvant endocrine therapy with goserelin and tamoxifen vs no endocrine therapy in premenopausal women with estrogen receptor–positive breast cancer. Benefit differed according to genomic risk status.
Study Details
In the trial, 924 patients were randomly assigned 1:1:1:1 between 1990 and 1997 to 2 years of goserelin at 3.6 mg subcutaneously once every 28 days, tamoxifen at 40 mg once daily, combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control group). Patients with node-positive disease received adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil).
Primary tumor immunohistochemistry and gene-expression profiling were performed in 2020. The 70-gene signature identified genomic low-risk and high-risk patients.
A total of 584 patients had estrogen receptor–positive disease, including 155 in the goserelin group, 135 in the tamoxifen group, 149 in the combination group, and 145 in the control group. Among patients with known genomic risk status, 305 patients had high risk and 158 low risk; risk was high vs low in 51 vs 80 patients in the goserelin group, 37 vs 69 in the tamoxifen group, 33 vs 85 in the combination group, and 37 vs 71 in the control group. Follow-up was 20 years.
Key Findings
In multivariate analysis among the 584 estrogen receptor–positive patients, long-term distant recurrence–free interval was significantly improved vs control with goserelin (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.32–0.75), tamoxifen (HR = 0.57, 95% CI = 0.38–0.87), and the combination (HR = 0.63, 95% CI = 0.42–0.94). Combination treatment was not associated with benefit vs tamoxifen alone (HR = 1.01, 95% CI = 0.65–1.58) or goserelin alone (HR = 1.27, 95% CI = 0.82–1.95). A significant goserelin-tamoxifen interaction was observed (P = .016).
Among genomic low-risk patients, a significant benefit was observed with tamoxifen vs control (HR = 0.24, 95% CI = 0.10–0.60), with numeric benefits not achieving significance for goserelin or the combination vs control. Among genomic high-risk patients, a significant benefit was observed with goserelin (HR = 0.24, 95% CI = 0.10–0.54), with numeric benefits not achieving significance for tamoxifen or the combination. Among high-risk patients, the combination was associated with significantly increased risk vs goserelin alone (HR = 3.36, 95% CI = 1.39–8.07).
Among genomic low-risk patients, a long-lasting benefit from tamoxifen was observed from year 4 to year 20 compared with control; hazard ratios were significant at years 5, 10, 15, and 20, with a hazard ratio of 0.23 (95% CI = 0.06–0.92) at year 20. Genomic high-risk patients derived early benefit from goserelin, with significant improvements vs control observed through the first 8 years; the hazard ratio at year 5 was 0.26 (95% CI = 0.11-0.61).
The investigators concluded: “This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor–positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.”
Annelie Johansson, MSc, PhD, Department of Oncology and Pathology, Karolinska Institutet and University Hospital, Stockholm, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Swedish Research Council, Swedish Cancer Society, California Breast Cancer Research Program, U.S. National Institutes of Health, and others. For full disclosures of the study authors, visit ascopubs.org.
