Effect of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density

Inclusion criteria

• Premenopausal women (defined as having at least one menstruation during the prior 12 months; women with an intrauterine device are considered premenopausal if <52 years)
• Women of childbearing potential using a highly effective method of birth control* throughout the study period and willing to comply with monthly pregnancy testing
• Screening mammogram performed within 3 month of study inclusion
• Mammographic density assessed as BI-RADS® score B, C, or D
• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects

Exclusion criteria

• Mammographic BI-RADS® malignancy code ≥3 at baseline mammography
• Any previous diagnosis of breast cancer, including carcinoma in situ, or any other cancer (non-melanoma skin cancer and in situ cancer of the cervix are not exclusion criteria)
• A history of breast surgery, e.g., reduction or enlargement, which might affect mammographic density measurements
• Current medical conditions:

• APC (activated protein C) resistance, an inherited coagulation disorder
• Systolic pressure higher than 160 mm Hg or diastolic higher than 100 mm Hg
• Cataract(s)
• Uncontrolled diabetes (defined as HbA1c >50 mmol/mol)
• Abnormal lab values deemed clinically significant by Investigator
• BMI > 30
• Women who have an increased risk of venous thrombosis due to immobilization, e.g., using wheelchair
• Agents that have the potential to decrease endoxifen levels through increased metabolic clearance:

• Certain anti-epileptic therapies (carbamazepine, fenytoin, fenobarbital, lamotrigine)
• Certain antibiotics (rifamycins)
• St John's wort (in Swedish: johannesört)
• Certain HIV medications (efavirenz, ritonavir)
• Lactating, pregnant, or plan to become pregnant in the next year
• History of thromboembolic disease such as embolus, deep vein thrombosis, stroke, TIA (transient ischemic attack) or myocardial infarction
• Allergy to endoxifen or any of its components
• Previous treatment with an anti-oestrogen, including experimental drug studies (e.g., Karma CREME, Karisma-1 or Karisma-2)
• Prescribed and regular use of anticoagulants (defined as substances included in group B01A in the ATC-system)
• Participation in another investigational clinical trial in the last 6 months
• Not willing or able to understand the study information and/or informed consent