The mammographic density reduction in healthy women, within the Karma cohort for five different doses of tamoxifen.
Conditions
Interventions
Product Name: Tamoxifen
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Product Name: Tamoxifen
Pharmaceutical Form: Tablet
Pha
Sponsors
Karolinska Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Attending the national mammography screening program, i.e. aged 40-74 and has performed a 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 950 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250
Exclusion criteria
Exclusion criteria: • Being pregnant or planning to become pregnant during the study period • 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 • A history of 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Identify the minimal dose of tamoxifen non-inferior in its ability to reduce mammographic density and with less side effects compared to 20 mg of tamoxifen.;Secondary Objective: Relate levels of tamoxifen metabolites, proteins, lipids and hormones in blood and changes in breast tissue to different tamoxifen doses. Measure genetic polymorphism in germline DNA and relate it to the other secondary objectives. Measure mammographic density and levels of side effects 6 months after tamoxifen cessation in relation to treatment arm.;Primary end point(s): Change in mammographic density and levels of side effects after 6 months.;Timepoint(s) of evaluation of this end point: 6 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Tamoxifen metabolites, proteins, lipids and hormones in blood. Breast tissue changes. Genetic polymorphism in germline DNA. Mammographic density and levels of side effects 6 months after tamoxifen cessation.;Timepoint(s) of evaluation of this end point: 6 months. | — |
Countries
Sweden
Contacts
Public ContactKarma Study Center
Södersjukhuset
Outcome results
None listed