{"doi":"10.1093/jnci/djae268","title":"Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial","abstract":"BACKGROUND: Estrogen receptor-positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up. METHODS: Secondary analysis of 1242 estrogen receptor-positive and HER2-negative patients that were randomly assigned to 2-5 years of 40 mg adjuvant tamoxifen or no endocrine therapy. Distant recurrence-free interval in tamoxifen-treated vs endocrine untreated patients was assessed by Kaplan-Meier, Cox proportional hazards regression, and time-varying analyses. RESULTS: In premenopausal patients, a statistically significant tamoxifen benefit was observed for lymph node-negative (adjusted hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.87), progesterone receptor-positive (adjusted HR = 0.61, 95% CI = 0.41 to 0.91), and genomic low-risk tumors (adjusted HR = 0.47, 95% CI = 0.26 to 0.85) but only lasted beyond 10 years for genomic low-risk tumors. Postmenopausal patients showed long-term benefit for all good-prognosis markers including low-grade (adjusted HR = 0.55, 95% CI = 0.41 to 0.73), lymph node-negative (adjusted HR = 0.44, 95% CI = 0.30 to 0.64), progesterone receptor-positive (adjusted HR = 0.60, 95% CI = 0.44 to 0.80), Ki-67 low (adjusted HR = 0.51, 95% CI = 0.38 to 0.68), and genomic low-risk tumors (adjusted HR = 0.53, 95% CI = 0.37 to 0.74), and regardless of tumor size (≤20 mm: adjusted HR = 0.55, 95% CI = 0.39 to 0.77; >20 mm: adjusted HR = 0.64, 95% CI = 0.44 to 0.94). Premenopausal patients with no poor-prognosis tumor characteristics (clinical marker score = 0) showed early benefit and postmenopausal long-term benefit. CONCLUSIONS: Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.","journal":"JNCI Journal of the National Cancer Institute","year":2024,"id":449714,"datarank":0.3935304128849984,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.12476649250079014,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.12476649250079014,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":711474,"name":"Huma Dar","orcid":"0000-0003-0710-1448","position":1,"is_corresponding":false},{"id":711476,"name":"Anna Nordenskjöld","orcid":"0000-0002-9123-4931","position":2,"is_corresponding":false},{"id":712332,"name":"Gizeh Pérez‐Tenorio","orcid":null,"position":3,"is_corresponding":false},{"id":797292,"name":"Nicholas P. Tobin","orcid":"0000-0003-2343-9772","position":4,"is_corresponding":false},{"id":14257,"name":"Christina Yau","orcid":"0000-0002-1937-0859","position":5,"is_corresponding":false},{"id":1907,"name":"Christopher C. Benz","orcid":"0000-0001-5479-4641","position":6,"is_corresponding":false},{"id":74873,"name":"Laura J. Esserman","orcid":"0000-0001-9202-4568","position":7,"is_corresponding":false},{"id":95644,"name":"L. J. van ‘t Veer","orcid":"0000-0002-9838-8298","position":8,"is_corresponding":false},{"id":711478,"name":"Bo Nordenskjöld","orcid":"0000-0002-2134-7586","position":9,"is_corresponding":false},{"id":600878,"name":"Olle Stål","orcid":"0000-0002-8290-0592","position":10,"is_corresponding":false},{"id":601443,"name":"Tommy� Fornander","orcid":null,"position":11,"is_corresponding":false},{"id":666890,"name":"Linda S. Lindström","orcid":"0000-0002-7722-7532","position":12,"is_corresponding":false},{"id":711475,"name":"Annelie Johansson","orcid":"0000-0001-9029-1996","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:02:20.585759Z","pmid":"39656627","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}