Karolinska Interventional Study of Mammograhic Density (Karisma-1)

Study Overview
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Brief Summary
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A feasibility study, randomising to either 10 or 20 mg of tamoxifen. The primary aim is to identify the time to mammographic density change and piloting the procedures. It is known that a density change is seen after 12 months of 20 mg of tamoxifen, but the clinical experience indicates that an effect of drugs influencing mammographic density could be seen already after a few months. The second aim is to evaluate if there is a density change from 10 mg of tamoxifen equivalent to 20 mg.

Detailed Description
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The investigators want to conduct a feasibility study including 42 women who will be randomised to either 10 or 20 mg of daily oral tamoxifen. The primary aim of the study is to identify the time to mammographic density change and piloting the procedures. It is known that a density change is seen after 12 months of 20 mg of daily tamoxifen, but the clinical experience indicates that an effect of drugs influencing mammographic density could be seen already after a few months. The second aim of the pilot study is to see if there is a density change from 10 mg of tamoxifen equivalent to 20 mg and if there is a difference in adverse reactions between the two doses. Interim analysis will be performed at 6 months, monitoring both safety and level of mammographic density change.

Official Title
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A Randomized, Open Pilot Study to Investigate the Mammographic Density Reduction on Healthy Women, Within the Karma Cohort, for Two Different Doses of Tamoxifen

Conditions
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Breast Cancer, Mammographic Density

Intervention / Treatment
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* Drug: Tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously participated in the Karma study Attending the national mammography screening program, i.e. aged 40-74 A mammogram, including a stored raw image, must have been taken within 3 weeks of baseline and start of therapy Having a mammographic volumetric density above the lowest 1/6, measured by Volpara Informed consent must be signed before any study specific assessments have been performed Exclusion Criteria: Being pregnant or planning to become pregnant during the study Any previous or current diagnosis of breast cancer (including carcinoma in situ) Recalled (mammographic code 3 or above) after baseline screening mammography Any previous diagnosis of cancer, with the exception of non-melanoma skin cancer and in situ cancer of the cervix Currently using 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 thromboembolic disease such as embolism, deep vein thrombosis, stroke, TIA or cardiac arrest. A history of immobilization, e.g. using wheelchair Uncontrolled diabetes defined as known untreated 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 paroxetine, fluoxetine and bupropion

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Clinical Trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifen 10mg<br>Randomised dose of daily oral Tamoxifen 10mg, for 180 days | Drug: Tamoxifen<br>* A registered SERM drug, Tamoxifen.<br>|
| Active Comparator: Tamoxifen 20mg<br>Randomised dose of daily oral Tamoxifen 20mg, for 180 days | Drug: Tamoxifen<br>* A registered SERM drug, Tamoxifen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to mammographic density change | Mammographic density followed on repeated mammographies by measurements using STRATUS software | Mammography after 0, 3, 6, 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in density change with tamoxifen 10 mg and 20 mg | Determine any differences in density change comparing 10 mg and 20 mg of daily oral tamoxifen. | Mammography after 0, 3, 6 months | 
| Differences in and adverse events with tamoxifen 10 mg and 20 mg | Determine any differences in adverse events comparing 10 mg and 20 mg of daily oral tamoxifen. | Questionnaires after 0, 1, 3, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tamoxifen, Low-dose, Randomized Clinical Trial