Breast Cancer
Conditions
Keywords
breast cancer chemoprevention, vitamin D, breast density
Brief summary
This is a phase II study which will enroll 20 postmenopausal women who are at high risk for breast cancer development. The goal is to determine whether a one-year intervention of high-dose vitamin D at 2 different doses (20,000 IU weekly or 30,000 IU weekly) will increase circulating blood levels of vitamin D and to obtain preliminary data on the biologic effects of vitamin D for breast cancer prevention.
Detailed description
Participants will receive oral vitamin D3, cholecalciferol 20,000 IU or 30,000 IU weekly. Before beginning the intervention, the participants will have a general physical exam including a clinical breast exam and anthropometric measures, a morning blood draw (for analysis of 25(OH)D, 1,25(OH)D, parathyroid hormone (PTH), insulin-like growth factor (IGF)-I, insulin-like growth factor-binding protein 3 (IGFBP-3), estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG) at baseline, 6 months, and 12 months) and a bilateral mammogram (at baseline and 12 months). Participants will also complete a baseline questionnaire, collecting data on demographic information and breast cancer risk factors. In addition, we will be collecting data on vitamin D sources from diet and sunlight exposure using a validated questionnaire administered at baseline and 12 months. For follow-up visits, the participant will be seen at the study site at months 3, 6, 9, and 12. During these visits, drug will be dispensed, adherence ascertained, and adverse events will also be assessed. In addition, blood (serum calcium, albumin, creatinine) and urine (urine calcium, creatinine) will be collected to monitor for toxicity. A 24-hour urine collection will be conducted at baseline and 12 months to assess for hypercalciuria. After the 1 year intervention, all participants will have a complete physical exam including clinical breast exam, a bilateral mammogram, blood draw, and complete a follow-up questionnaire.
Interventions
DRUGCholecalciferol
Cholecalciferol is a vitamin D3. Vitamin D is important for the absorption of calcium from the stomach and for the functioning of calcium in the body. Cholecalciferol is used to treat or prevent many conditions caused by a lack of vitamin D. Cholecalciferol will be available in gel capsule form at 10,000 IU (0.25 mg cholecalciferol) each.
DRUGPlacebo capsule
Matching placebo capsules
Sponsors
Avon Foundation
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Elevated risk of breast cancer defined as having at least one of the following: (1) Predicted 5-year modified Gail model risk of 1.67% or greater, (2) Lobular carcinoma in situ, (3) Known BRCA1 or BRCA2 deleterious mutation carrier, (4) Prior history of ductal carcinoma in situ, if no current tamoxifen use or prior radiation to the contralateral breast. * Age 21 years or older. * Postmenopausal defined as \> 6 months since the last menstrual period, prior bilateral oophorectomy, or serum follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values consistent with institutional normal values for the postmenopausal state. * Baseline mammographic density ≥25% as assessed qualitatively by the mammographer (25-50% = scattered fibroglandular densities; \>50-75% = heterogeneously dense breasts; \>75% = extremely dense breasts). * Baseline serum 25-hydroxyvitamin D \<32 ng/ml. * Normal breast exam and mammogram (Breast Imaging Reporting and Data System (BIRADS) score of 1 or 2) or abnormal breast imaging with a benign breast biopsy without evidence of cancer. Normal baseline breast magnetic resonance imaging (MRI) (BIRADS score of 1, 2, or 3). * Prior tamoxifen or raloxifene use is allowed provided treatment is discontinued at least 28 days prior to enrollment. * At least one breast available for imaging. No bilateral breast implants. * Willingness to not take vitamin D supplements during the one year intervention, but up to 1000mg of calcium supplementation is allowed. * Normal serum calcium. * Adequate renal and hepatic function: serum creatinine, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase \< 2.0 x the institutional upper limit of normal (IULN). * Performance status of 0 or 1.
Exclusion criteria
* Other prior malignancy. The following is allowed: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer (including breast cancer) for which the participant has been disease-free for 5 years. * History of kidney stones. * Hypersensitivity reactions to vitamin D. * On estrogen replacement therapy. * Significant medical or psychiatric condition that would preclude study completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum 25(OH)D | Baseline to 1 year | 25(OH)D level at the end of one year intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Density | Baseline to 1 year | Assessed by mammography and breast MRI. |
Countries
United States
Participant flow
Pre-assignment details
Data for this study (NCT00859651; n=20 postmenopausal; 8 received 20,000 IU/week and 12 received 30,000 IU/week) is combined with the data for another study (NCT00976339; n=20 premenopausal; 10 received 20,000 IU/week and 10 received 30,000 IU/week). Resulting in a combination of 18 receiving 20,000 IU/week and 22 receiving 30,000 IU/week.
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 20,000 IU Group Postmenopausal women who are at increased risk for breast cancer development receiving vitamin D3, oral cholecalciferol 20,000 IU weekly, for one year. | 18 |
| Cholecalciferol 30,000 IU Group Postmenopausal women who are at increased risk for breast cancer development receiving vitamin D3, oral cholecalciferol 30,000 IU weekly, for one year. | 22 |
| Total | 40 |
Baseline characteristics
| Characteristic | Cholecalciferol 20,000 IU Group | Cholecalciferol 30,000 IU Group | Total |
|---|---|---|---|
| Age, Continuous | 50.0 years | 50.5 years | 50 years |
| Region of Enrollment United States | 18 participants | 22 participants | 40 participants |
| Sex: Female, Male Female | 18 Participants | 22 Participants | 40 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 | — / — | — / — |
| other Total, other adverse events | 14 / 18 | 22 / 22 |
| serious Total, serious adverse events | 0 / 18 | 0 / 22 |
Outcome results
Primary
Change in Serum 25(OH)D
25(OH)D level at the end of one year intervention
Time frame: Baseline to 1 year
Population: Data for this study (NCT00859651; n=20) is combined with the data for another study (NCT00976339; n=20).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol 20,000 IU Group | Change in Serum 25(OH)D | 25 ng/ml | Standard Deviation 5 |
| Cholecalciferol 30,000 IU Group | Change in Serum 25(OH)D | 33 ng/ml | Standard Deviation 9 |
Secondary
Change in Percent Density
Assessed by mammography and breast MRI.
Time frame: Baseline to 1 year
Population: Data for this study (NCT00859651; n=20) is combined with the data for another study (NCT00976339; n=20).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol 20,000 IU Group | Change in Percent Density | 3 percentage of breast density | Standard Deviation 1 |
| Cholecalciferol 30,000 IU Group | Change in Percent Density | 1 percentage of breast density | Standard Deviation 1 |