Vitamin D in Postmenopausal Women at High Risk for Breast Cancer

Effects of High-Dose Vitamin D on Circulating Vitamin D Levels and Breast Density in Postmenopausal Women at High Risk for Breast Cancer Development

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Cholecalciferol; Drug: Placebo capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 20,000 IU weekly; Postmenopausal women who are at increased risk for breast cancer development receiving vitamin D3, oral cholecalciferol 20,000 IU weekly, for one year. Cholecalciferol 20,000 IU (2 active capsules + 1 matching placebo capsule)	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 Names: Vitamin D3; Drug: Placebo capsule; Matching placebo capsules; Other Names: Placebo
ACTIVE_COMPARATOR: 30,000 IU weekly; Postmenopausal women who are at increased risk for breast cancer development receiving vitamin D3, oral cholecalciferol 30,000 IU weekly, for one year. Cholecalciferol 30,000 IU (3 active capsules)	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 Names: Vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum 25(OH)D	25(OH)D level at the end of one year intervention	Baseline to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent Density	Assessed by mammography and breast MRI.	Baseline to 1 year

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Avon Foundation

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 9, 2009
• First Posted (ESTIMATE): March 11, 2009

Study Record Updates

• Last Update Posted (ACTUAL): September 27, 2017
• Last Update Submitted That Met QC Criteria: August 30, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: vitamin D; breast density; breast cancer chemoprevention
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: AAAD3638

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No