Breast Cancer
Conditions
Keywords
Breast cancer, Vitamin D, Premenopausal
Brief summary
This proposal is for a pilot study of 20 premenopausal women at high risk for breast cancer development who will receive high dose vitamin D3, cholecalciferol 20,000 IU (2 capsules) weekly, or 30,000 IU (3 capsules) weekly, for 1 year. The primary objective of this study is to determine the feasibility of a 1-year intervention of vitamin D in this study population. Secondary objectives include evaluating the biologic effects of vitamin D supplementation on blood based and image-based biomarkers.
Detailed description
Vitamin D has diverse biological effects relevant to carcinogenesis, including known cross-talk between the vitamin D receptor (VDR) and insulin-like growth factor (IGF) signaling pathways. Based upon observational data, women with serum 25(OH) D levels greater than 40-50 ng/ml had a 50% lower risk of breast cancer compared to women with vitamin D deficiency. Vitamin D is a fat-soluble vitamin which is produced in the body and may come from food sources. Epidemiologic studies suggest that vitamin D may influence breast cancer development, which has resulted in increased interest in the use of vitamin D for the treatment and prevention of breast cancer. Numerous experimental studies have shown that vitamin D compounds have anti-carcinogenic properties against breast cancer. Given the epidemiologic data and the extensive preclinical evidence of the anti-tumor effects of vitamin D, it is therefore reasonable to test the biological effects of high-dose vitamin D in early phase clinical trials. The investigators hypothesize that vitamin D3, cholecalciferol, will modulate biomarkers of breast cancer risk. The relationship between vitamin D status and mammographic density (MD), a strong predictor of breast cancer risk, remains unclear \[8\]. MD refers to the relative proportions of radiolucent fat and radiodense epithelial and stromal tissue and may serve as a useful intermediate biomarker for breast cancer risk assessment in investigations of potential chemopreventive agents. Cross-sectional studies evaluating the association between vitamin D intake and MD observed an inverse association among premenopausal women, particularly with high serum IGF-1 and low serum IGF binding protein-3 (IGFBP-3). However, there is limited data on the biologic effects of vitamin D supplementation for breast cancer prevention in human intervention trials.
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.
Sponsors
Prevent Cancer Foundation
Katherine D. Crew
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
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 1.7% 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. * Premenopausal defined as \< 6 months since the last menstrual period, no prior bilateral oophorectomy, not on estrogen replacement, and serum Follicle-stimulating hormone (FSH) values consistent with institutional normal values for the premenopausal state. * Normal breast exam and mammogram (BIRADS score of 1 or 2). * 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. * Prior tamoxifen use is allowed provided treatment is discontinued at least 28 days prior to enrollment. * Willingness to allow submission of core needle breast biopsy for pathology review and collection of blood for biomarker analysis and banking. * At least one breast available for imaging and biopsy. * Willingness to not take calcium or vitamin D supplements during the one year intervention, due to the potential risk of hypercalcemia/hypercalciuria with high dose vitamin D. Premenopausal women who need to take calcium supplementation for any medical condition will be excluded from the study. Dietary restrictions on calcium intake may be imposed if the subject is found to have borderline high serum or urine levels of calcium during the study intervention and a list of dietary sources of calcium will be provided. * Normal serum calcium. * No history of kidney stones. * Adequate renal and hepatic function: serum creatinine, bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase \< 2.0 x the institutional upper limit of normal (IULN). * No hypersensitivity reactions to vitamin D. * Performance status of 0 or 1. * Not pregnant or nursing. * Agree to use effective contraception, hormone-based oral contraceptives allowed but switching birth control methods is discouraged while on-study. * No significant medical or psychiatric condition that would preclude study completion.
Exclusion criteria
* Not meeting one or any of inclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants That Successfully Completed the 1-year Intervention | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Change in Mammographic Breast Density | 1 year |
Countries
United States
Participant flow
Recruitment details
Referrals to the Columbia breast oncology clinic for breast cancer chemoprevention will be recruited medical oncologist or via recruitment flyers. Recruitment letters will be sent to high-risk women who participated in the Metropolitan Breast Cancer Family Registry and Women at Risk (WAR) database.
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 20,000 IU Subjects received Cholecalciferol 20,000 IU weekly, for 1 year | 10 |
| Cholecalciferol 30,000 IU Subjects received Cholecalciferol 30,000 IU weekly, for 1 year | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Cholecalciferol 20,000 IU | Cholecalciferol 30,000 IU | Total |
|---|---|---|---|
| Age, Customized > 21 years | 10 Participants | 10 Participants | 20 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 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 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Participants That Successfully Completed the 1-year Intervention
Time frame: 1 year
Population: Data for this study (NCT00976339) is combined with the data for another study (NCT00859651); see NCT00859651 for combined results. Investigator is unable to determine the subject data that should be entered for this study alone, since subject data was combined for the purpose of data analysis. Data for this study alone was not analyzed.
Secondary
Change in Mammographic Breast Density
Time frame: 1 year
Population: Data for this study (NCT00976339) is combined with the data for another study (NCT00859651); see NCT00859651 for combined results. Investigator is unable to determine the subject data that should be entered for this study alone, since subject data was combined for the purpose of data analysis. Data for this study alone was not analyzed.