The KARISMA Tamoxifen trials are interventional trials exploring new alternatives for primary prevention of breast cancer.
The aim of the KARISMA Tamoxifen 2 trial was to find out if lower doses of tamoxifen have fewer side effects without lowering the risk-reducing effect. Tamoxifen has been used to prevent breast cancer recurrence in patients for >30 years. Healthy women who take tamoxifen 20 mg daily for 5 years get a 30-40% reduced risk of breast cancer, but the medication may cause side effects. Common side effects of tamoxifen are hot flashes, sweating, weight gain, vaginal discharge, etc.
From February 2017 to March 2019 1,440 women were recruited at the South General Hospital, Stockholm. All women attending the national mammography screening program were invited. After informed consent participants were randomized to 20, 10, 5, 2.5, 1 mg of tamoxifen and placebo. Outcome was change in mammographic density and women were treated for 6 month.
A decrease in mammographic density is a proxy for a reduced risk of developing breast cancer. The primary results of 2.5 mg of tamoxifen giving an equal decrease in mammographic density was published in March 2021 (see Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial; https://karmastudy.org/publication/.
In addition to the primary endpoint on treatment effect we closely followed the side effect panorama. Analyses are ongoing and will be published.
We also measured metabolites of tamoxifen, such as Z-endoxifen, and polymorphism of key metabolizing genes (e.g CYP2D6) and female sex hormones. The first publication with CYP2D6 results was published in October 2021 (CYP2D6 genotype predicts tamoxifen discontinuation and drug response: a secondary analysis of the KARISMA Tamoxifen trial; https://karmastudy.org/publication/)
Almost one hundred of the KARISMA Tamoxifen 2 participants also volunteered for a sub-study with breast biopsies before and after treatment. Analyses are ongoing and will be published.