Clinical trial · Interventional
Low Dose Tamoxifen for Mammographic Density Reduction
A Randomised, Double Blinded, Six-armed Placebo Controlled Study to Investigate Optimal Dose of Tamoxifen With the Most Favourable Side Effect Spectre and With Mammography Density Reduction Non-inferior to That of 20 mg Tamoxifen
NCT03346200CI-TRIAL-00086879KARISMA2completedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
KARISMA2 is a randomized, double-blinded, six-armed placebo controlled study to identify a low dose of tamoxifen, with less side-effects and a density reduction non-inferior to the standard dose of 20 mg.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Mammographic Density Reduction | — | UNRESOLVED | — |
| Risk Reduction | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Placebo Oral Tablet | Drug | — | UNRESOLVED |
| Tamoxifen Oral Tablet | Drug | Tamoxifen | ALIAS |
Design
Arms and outcomes
Arms (6)
- type
- ACTIVE_COMPARATOR
- label
- 20 mg tamoxifen
- interventionNames
- Drug: Tamoxifen Oral Tablet
- type
- EXPERIMENTAL
- label
- 10 mg tamoxifen
- interventionNames
- Drug: Tamoxifen Oral Tablet
- type
- EXPERIMENTAL
- label
- 5 mg tamoxifen
- interventionNames
- Drug: Tamoxifen Oral Tablet
- type
- EXPERIMENTAL
- label
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 40 Years
- Maximum age
- 74 Years
Show eligibility criteria text
Inclusion Criteria: * Attending the national mammography screening program, i.e. aged 40-74 and has performed a screening mammogram maximum 3 months prior to study inclusion * Having a measurable mammographic density, i.e. ≥4.5 % density (volumetric) measured by Volpara * Informed consent must be signed before any study specific assessments have been performed Exclusion Criteria: * Pregnancy at start, during time of study medication and up to 3 months after quitting study medication * Breast feeding at start, during time of study medication and up to 3 months after quitting study medication * Any previous or current diagnosis of breast cancer (including carcinoma in situ) * Mammographic BI-RADS code 3 or above at baseline mammography, or at a diagnostic mammography during time of treatment (the first 6 months of the study) * Any previous diagnosis of cancer with the exception of non-melanoma skin cancer and in situ cancer of the cervix * Currently using oral oestrogen and progesterone based hormone replacement therapy * Current use of hormone contraceptive with hormones, e.g. hormonal contraceptive pills, or progesterone implants. Hormonal intrauterine devices are accepted. * A history of thrombo-embolic disease such as embolies, deep vein thrombosis, stroke, TIA or cardiac arrest. * Known APC (Activated protein C )- resistance, an inherited hemostatic disorder * A history of major surgery of the breast, e.g. reduction or enlargement, which might affect density measurements * Women who have an increased risk of venous thrombosis due to immobilization, e.g. using wheelchair * Known uncontrolled diabetes * Hypertension at baseline, defined as systolic pressure higher than 140 mm Hg and diastolic higher than 90 mm Hg * Use of drugs that interfere with CYP2D6 expression such as Seroxat (paroxetine), Fontex (fluoxetin) and Zyban / Voxra (bupropion) * Use of Waran (warfarin) * Non-medical approved drugs against hot-flashes including phytooestrogen * Not able to understand study information and/or informed consent
References
Publications (5)
- RESULTEriksson M, Eklund M, Borgquist S, Hellgren R, Margolin S, Thoren L, Rosendahl A, Lang K, Tapia J, Backlund M, Discacciati A, Crippa A, Gabrielson M, Hammarstrom M, Wengstrom Y, Czene K, Hall P. Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial. J Clin Oncol. 2021 Jun 10;39(17):1899-1908. doi: 10.1200/JCO.20.02598. Epub 2021 Mar 18. PMID 33734864
- DERIVEDGoransson S, Hernandez-Varas P, Hammarstrom M, Hellgren R, Backlund M, Lang K, Rosendahl AH, Eriksson M, Borgquist S, Stromblad S, Czene K, Hall P, Gabrielson M. Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial. Breast Cancer Res. 2024 Nov 26;26(1):163. doi: 10.1186/s13058-024-01919-1. PMID 39593191
- DERIVEDGabrielson M, Hammarstrom M, Bergqvist J, Lang K, Rosendahl AH, Borgquist S, Hellgren R, Czene K, Hall P. Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change. Int J Cancer. 2024 Jul 15;155(2):339-351. doi: 10.1002/ijc.34939. Epub 2024 Mar 30. PMID 38554131
- DERIVEDHammarstrom M, Gabrielson M, Crippa A, Discacciati A, Eklund M, Lundholm C, Backlund M, Wengstrom Y, Borgquist S, Bergqvist J, Eriksson M, Tapia J, Czene K, Hall P. Side effects of low-dose tamoxifen: results from a six-armed randomised controlled trial in healthy women. Br J Cancer. 2023 Jul;129(1):61-71. doi: 10.1038/s41416-023-02293-z. Epub 2023 May 6. PMID 37149701
- DERIVEDGabrielson M, Hammarstrom M, Backlund M, Bergqvist J, Lang K, Rosendahl AH, Borgquist S, Hellgren R, Czene K, Hall P. Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women. Int J Cancer. 2023 Jun 1;152(11):2362-2372. doi: 10.1002/ijc.34430. Epub 2023 Jan 22. PMID 36637153