Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.

TitleTwenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.
Publication TypeJournal Article
Year of Publication2022
AuthorsJohansson, A, Dar, H, Veer, LJ van 't, Tobin, NP, Perez-Tenorio, G, Nordenskjöld, A, Johansson, U, Hartman, J, Skoog, L, Yau, C, Benz, CC, Esserman, LJ, Stål, O, Nordenskjöld, B, Fornander, T, Lindström, LS
JournalJ Clin Oncol
Volume40
Issue35
Pagination4071-4082
Date Published2022 Dec 10
ISSN1527-7755
KeywordsBreast Neoplasms, Female, Genomics, Goserelin, Humans, Middle Aged, Premenopause, Receptors, Estrogen, Tamoxifen
Abstract

PURPOSE: To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.

METHODS: Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years.

RESULTS: In estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed ( = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit.

CONCLUSION: 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.

DOI10.1200/JCO.21.02844
Alternate JournalJ Clin Oncol
PubMed ID35862873
PubMed Central IDPMC9746735
Grant ListU01 CA196406 / CA / NCI NIH HHS / United States