Karolinska Interventional Study of Mammograhic Density (Karisma-1)

Phase 1

Completed

• Conditions: Breast Cancer; Mammographic Density
• Interventions: Drug: Tamoxifen

• Registration Number: NCT04079517
• Lead Sponsor: Karolinska Institutet

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-03
• Primary Completion: 2016-02
• Study Completion: 2016-03
• Study First Submitted: 2019-09-03
• Study First Submitted QC: 2019-09-03
• Study First Posted: 2019-09-06
• Results First Submitted: 2024-06-20
• Status Verified: 2025-02
• Results First Submitted QC: 2025-02-05
• Last Update Submitted: 2025-02-05
• Results First Posted: 2025-02-06
• Last Update Posted: 2025-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tamoxifen 20mg	Tamoxifen	Randomised dose of daily oral Tamoxifen 20mg, for 180 days
Tamoxifen 10mg	Tamoxifen	Randomised dose of daily oral Tamoxifen 10mg, for 180 days

Primary Outcome Measures

Name	Time	Method
Mammographic Breast Density	6 months	Mean change in mammographic breast density at 6 months compared to baseline (=0 months) for each dose arm, using the fully automated STRATUS method. The average percent density (fibroglandular dense tissue area divided by total breast area) of left and right breasts at baseline was calculated and compared with average percent density at the end of the trial period and density change was defined as the difference between these two measures.

Secondary Outcome Measures

Name	Time	Method
Symptom Score	9 months	Symptom score change, compared to baseline for each dose arm. Questionnaires were used at 0, 1, 3, 6, 9 months. Vasomotor, gynecological, sexual, and musculoskeletal symptoms were assessed using a 5-grade Likert severity scale ranging from "no symptom at all" to "very much symptoms". A higher symptom score equals less symptoms, i.e. a better outcome.; The questionnaire was based on the Functional Assessment of Cancer Therapy - Endocrine Subscale 7 (FACT-ES.7).; The presented score was calculated as the sum of the last month's symptom severity levels and are presented as the absolute differences in symptom score on a scale ranging from any minus five to any plus five. A higher symptom score equals less symptoms, i.e. a better outcome.