Study of Vitamin D for Premenopausal Women at High Risk for Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00976339
Recruitment Status : Completed
First Posted : September 14, 2009
Results First Posted : June 15, 2016
Last Update Posted : September 29, 2017
Prevent Cancer Foundation
Information provided by (Responsible Party):
Katherine D. Crew, Columbia University

September 11, 2009
September 14, 2009
July 27, 2015
June 15, 2016
September 29, 2017
September 2007
December 2013   (Final data collection date for primary outcome measure)
Number of Participants That Successfully Completed the 1-year Intervention [ Time Frame: 1 year ]
Safety and Feasibility [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00976339 on Archive Site
Change in Mammographic Breast Density [ Time Frame: 1 year ]
Histologic changes, Mammographic Density, and Biological Correlates [ Time Frame: 2 years ]
Not Provided
Not Provided
Study of Vitamin D for Premenopausal Women at High Risk for Breast Cancer
Pilot Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer
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.

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.

Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Breast Cancer
Drug: Cholecalciferol

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.

Other Name: Vitamin D3
  • Experimental: Cholecalciferol 20,000 IU
    Participants will receive Cholecalciferol 20,000 IU (2 capsules) weekly for one year.
    Intervention: Drug: Cholecalciferol
  • Experimental: Cholecalciferol 30,000 IU
    Participants will receive Cholecalciferol 30,000 IU (3 capsules) weekly for one year.
    Intervention: Drug: Cholecalciferol

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
December 2013
December 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Female
21 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Katherine D. Crew, Columbia University
Katherine D. Crew
Prevent Cancer Foundation
Principal Investigator: Katherine Crew, MD Columbia University
Columbia University
August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP