Low Dose Tamoxifen for Mammographic Density Reduction

Summary

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.

Timeline

Start

2016-11

Primary completion

2019-10

Completion

2019-12

Outcome

Met primary endpoint

registry analysis (non-inferiority test); 20 mg Tamoxifen; p <0.01; Median Difference (Final Values) 52.5 (97.5% CI 41.9 to 100); one-sided Wald tests NCT03346200 ↗

paper Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen PMID 33734864 ↗

Publications

• Results Eriksson 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.
• Goransson 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.
• Gabrielson 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.
• Hammarstrom 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.
• Gabrielson 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Tamoxifen	Small molecule	1 mg	Oral
Subject	Tamoxifen	Small molecule	2.5 mg	Oral
Subject	Tamoxifen	Small molecule	5 mg	Oral
Subject	Tamoxifen	Small molecule	10 mg	Oral
Subject	Tamoxifen	Small molecule	20 mg	Oral

Indications