This trial is active, not recruiting.

Condition breast cancer
Treatments cholecalciferol
Sponsor Katherine D. Crew
Collaborator Prevent Cancer Foundation
Start date September 2007
End date July 2013
Trial size 20 participants
Trial identifier NCT00976339, AAAC3089


Despite significant advances in the early detection and treatment of breast cancer, it is still the most common cancer among women in the U.S. and up to 25% will die of their disease. Therefore, more attention has focused on primary prevention to reduce breast cancer-related morbidity and mortality. Due to the limited number of significant modifiable risk factors for breast cancer, researchers are exploring the potential of chemoprevention to arrest or reverse cancer development with a drug intervention. Currently, tamoxifen is the only FDA-approved drug for breast cancer risk reduction. However, tamoxifen's adverse effects have limited its usage. It is anticipated that raloxifene will be used more, as it has a more favorable side effect profile. However, tamoxifen and raloxifene do not prevent estrogen receptor (ER)-negative breast tumors, which account for about a third of all breast cancers and are associated with a poorer prognosis. Current priorities in breast cancer chemoprevention are to identify preventive agents which may be effective against ER-negative breast cancers, and have a low risk of side-effects.

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model single group assignment
Masking open label
Primary purpose prevention
Cohort 1 to take 30,000 IU Vitamin D weekly for one year
cholecalciferol Vitamin D3
Cholecalciferol (D3) 30,000 IU weekly for 1 year
Cohort 2 to take 20,000 IU Vitamin D weekly for one year
cholecalciferol Vitamin D3
Cholecalciferol (D3) 20,000 IU weekly for 1 year

Primary Outcomes

Safety and Feasibility
time frame: 2 years

Secondary Outcomes

Histologic changes, Mammographic Density, and Biological Correlates
time frame: 2 years

Eligibility Criteria

Female participants at least 21 years old.

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 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, AST, ALT and alkaline phosphatase < 2.0 x the institutional upper limit of normal (IULN). - No hypersensitivity reactions to vitamin D. - Zubrod 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

Additional Information

Official title Pilot Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer
Principal investigator Katherine Crew, MD
Description The investigators plan to conduct a pilot feasibility study in 20 premenopausal women who are at high risk for breast cancer development who will receive oral cholecalciferol (vitamin D3) 30,000 IU (n = 10) or 20,000 IU (n = 10) weekly for one year. Pretreatment and posttreatment mammograms, breast biopsies, and blood will be evaluated for a variety of biomarkers. The primary objective of this study is to determine the feasibility and toxicity associated with this 1-year intervention of vitamin D in this study population. The secondary objective is to obtain preliminary data on the biological effects of vitamin D on normal breast tissue. The results of this pilot study will be used to implement a larger multicenter trial of vitamin D for breast cancer chemoprevention.
Trial information was received from ClinicalTrials.gov and was last updated in February 2013.
Information provided to ClinicalTrials.gov by Columbia University.