Breast Cancer, Mammographic Density
Conditions
Keywords
Tamoxifen, Low-dose, Randomized Clinical Trial
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.
Interventions
DRUGTamoxifen
A registered SERM drug, Tamoxifen.
Sponsors
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized Clinical Trial
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 74 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tamoxifen 10mg Randomised dose of daily oral Tamoxifen 10mg, for 180 days
Tamoxifen: A registered SERM drug, Tamoxifen. | 23 |
| Tamoxifen 20mg Randomised dose of daily oral Tamoxifen 20mg, for 180 days
Tamoxifen: A registered SERM drug, Tamoxifen. | 19 |
| Total | 42 |
Baseline characteristics
| Characteristic | Tamoxifen 20mg | Total | Tamoxifen 10mg |
|---|---|---|---|
| Age, Continuous | 62.32 years STANDARD_DEVIATION 6.74 | 61.5 years STANDARD_DEVIATION 5.1 | 59.74 years STANDARD_DEVIATION 8.48 |
| Region of Enrollment Sweden | 19 participants | 42 participants | 23 participants |
| Sex: Female, Male Female | 19 Participants | 42 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 19 |
| other Total, other adverse events | 18 / 23 | 18 / 19 |
| serious Total, serious adverse events | 0 / 23 | 0 / 19 |
Outcome results
Primary
Mammographic Breast Density
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.
Time frame: 6 months
Population: The final analysis was restricted to the 19 plus 14 participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tamoxifen 10mg | Mammographic Breast Density | -3.3 percentage of breast area |
| Tamoxifen 20mg | Mammographic Breast Density | -2.5 percentage of breast area |
Secondary
Symptom Score
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.
Time frame: 9 months
Population: Participants answering baseline and 9 month questionnaires.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tamoxifen 10mg | Symptom Score | 1.8 score on a scale |
| Tamoxifen 20mg | Symptom Score | 3.7 score on a scale |