Evidence map›Paper›PMID 39656627›Full record

Trial reportJournal of the National Cancer Institute2025

Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial.

Annelie Johansson, Huma Dar, Anna Nordenskjöld, Gizeh Perez-Tenorio, Nicholas P Tobin, Christina Yau, Christopher C Benz, Laura J Esserman, Laura J van 't Veer, Bo Nordenskjöld and 3 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the National Cancer Institute, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Annelie JohanssonDepartment of Oncology and Pathology, Karolinska Institutet, 171 64 Stockholm, Sweden.ORCID 0000-0001-9029-1996
Huma DarDepartment of Oncology and Pathology, Karolinska Institutet, 171 64 Stockholm, Sweden.
Anna NordenskjöldInstitution of Clinical Sciences, Department of Oncology, Sahlgrenska Academy, Gothenburg University, 413 45 Gothenburg, Sweden.
Gizeh Perez-TenorioDepartment of Biomedical and Clinical Sciences and Department of Oncology, Linköping University, 581 83 Linköping, Sweden.
Nicholas P TobinDepartment of Oncology and Pathology, Karolinska Institutet, 171 64 Stockholm, Sweden.
Christina YauBuck Institute for Research on Aging, Novato, CA 94945, United States.ORCID 0000-0002-1937-0859
Christopher C BenzBuck Institute for Research on Aging, Novato, CA 94945, United States.ORCID 0000-0001-5479-4641
Laura J EssermanDepartment of Surgery, University of California San Francisco, San Francisco, CA 94115, United States.
Laura J van 't VeerDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94115, United States.
Bo NordenskjöldDepartment of Biomedical and Clinical Sciences and Department of Oncology, Linköping University, 581 83 Linköping, Sweden.
Olle StålDepartment of Biomedical and Clinical Sciences and Department of Oncology, Linköping University, 581 83 Linköping, Sweden.
Tommy FornanderDepartment of Oncology and Pathology, Karolinska Institutet, 171 64 Stockholm, Sweden.
Linda S LindströmDepartment of Oncology and Pathology, Karolinska Institutet, 171 64 Stockholm, Sweden.

Funding

Elucidating the molecular and contextual basis for IDLE ultralow risk lesions and the tumor immune microenvironment of high risk in situ and invasive breast cancersU01CA196406 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOROWSKY, ALEXANDER D, ESSERMAN, LAURA J · 2015 to 2020
$5.8M
ALF medicine FoUI-974882California Breast Cancer Research Program 180B-0065Cancerföreningen i Stockholm 221233Gösta Milton Donation FundKing Gustav V Jubilee Clinical Research Foundation 2021-356NIH HHS U01-CA196406Stiftelsen Gösta Miltons donationsfondStockholm Cancer SocietyStockholm Cancer Society 221233Swedish Cancer Society 222081Swedish Research CouncilSwedish Research Council 2020-02466Swedish Research Council for Health, Working life and Welfare 2019-00477Vetenskapsrådet 2020-02466
6 · The paper itself

Abstract

backgroundEstrogen 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.

methodsSecondary 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.

resultsIn 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.

conclusionsOur 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.

Indexed as

Antineoplastic Agents, HormonalBreast NeoplasmsMenopauseTamoxifenAdultAgedBiomarkers, TumorChemotherapy, AdjuvantErb-b2 Receptor Tyrosine KinasesFemaleFollow-Up StudiesHumansKaplan-Meier EstimateKi-67 AntigenMiddle AgedPostmenopauseAntineoplastic Agents, HormonalBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKi-67 AntigenReceptors, EstrogenReceptors, ProgesteroneTamoxifen

Identifiers

PMID39656627
PMCPMC12058260

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.