VITamin D and OmegA-3 TriaL: Effects on Mammographic Density and Breast Tissue (VITAL)

THE EFFECTS OF VITAMIN D ON MAMMOGRAPHIC DENSITY AND BREAST TISSUE

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing randomized clinical trial in 25,875 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study is being conducted among participants in VITAL and will examine whether vitamin D effects mammographic breast density, mammographic texture features, and gene expression profiles in breast biopsy tissue.

Study Overview

• Status: Active, not recruiting
• Conditions: Benign Breast Disease
• Intervention / Treatment: Dietary supplement: Vitamin D placebo and fish oil placebo; Dietary supplement: Fish oil and vitamin D placebo; Dietary supplement: Vitamin D and fish oil placebo; Dietary supplement: Vitamin D and fish oil

Detailed Description

Mammographic density is one of the strongest risk factors for breast cancer. It is predictive of breast cancer risk for at least 10 years in the futue and has been suggested as a surrogate marker of breast cancer risk. Several states now mandate release of mammographic density data to women. However, except for anti-hormonal therapies (e.g., tamoxifen), no interventions have been proven to reduce breast density. Thus, testing promising, well-tolerated interventions that might affect mammographic density is of substantial interest. Several lines of evidence suggest that vitamin D may play a role in breast density and breast carcinogenesis. Vitamin D reduces proliferation and promotes differentiation and apoptosis in breast cells in culture. However, no large-scale randomized studies have examined the impact of vitamin D on mammographic density. We propose to examine the randomized effects vitamin D3 on mammographic breast density in the NIH sponsored VITamin D and OmegA-3 TriaL (VITAL), an ongoing randomized, double blind, trial testing vitamin D3 (2,000 IU/day cholecalciferol) and omega-3 fatty acids (840 mg eicosapentaenoic acid [EPA]+ docosahexaenoic acid [DHA]) in the primary prevention of cancer and cardiovascular disease in a multi-ethnic population of over 24,000 men and women. In this ancillary sub study, mammograms will be obtained on 4000 women age 55-67 years (25% African-American), from baseline (pre-randomization) and after 1 and 4 years of randomized therapy. Centrally processed quantitative mammographic density and texture variation will be measured. We will determine if randomized vitamin D treatment is associated with change in mammographic features, and whether effects are modified by baseline mammographic density, and baseline 25(OH) vitamin D levels. In addition, tissue samples from women in VITAL undergoing breast biopsy/surgery, for both nonmalignant and malignant conditions, will be collected. Quantitative morphological measures, as well as gene expression assays targeting vitamin D activation and breast carcinogenesis pathways, will be performed on collected tissues among women on randomized vitamin D3 compared with placebo. This ancillary study provides a timely opportunity to test comprehensively the effects of vitamin D3 on mammographic features and breast tissue biology in a randomized setting at minimal additional cost.

• Study Type: Interventional
• Enrollment (Anticipated): 3894
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• part of parent VITAL trial

Exclusion Criteria:

• Men,
• women with breast cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vitamin D placebo and fish oil placebo; vitamin D placebo + fish oil placebo	Dietary supplement: Vitamin D placebo and fish oil placebo; placebo
Active Comparator: Fish oil and vitamin D placebo; Vitamin D placebo and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])	Dietary supplement: Fish oil and vitamin D placebo; 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]); Other Names: 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])
Active Comparator: Vitamin D and fish oil placebo; Vitamin D3 (cholecalciferol), 2000 IU per day and fish oil placebo	Dietary supplement: Vitamin D and fish oil placebo; Vitamin D3 (cholecalciferol), 2000 IU per day and fish oil placebo
Active Comparator: Vitamin D and fish oil; Vitamin D3 (cholecalciferol), 2000 IU per day and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])	Dietary supplement: Vitamin D and fish oil; Vitamin D3 (cholecalciferol), 2000 IU per day and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mammographic breast density	We will collect baseline (pre-randomization), 1-year and 4-year follow-up mammograms, as well as tissue specimens from women undergoing breast biopsy/surgery for malignant and nonmalignant disease, to further elucidate the role of vitamin D on mammographic features and breast tissue biology	change baseline to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast tissue	Quantitative morphological measures, as well as gene expression assays targeting vitamin D activation and breast carcinogenesis pathways, will be performed on collected tissues among women on randomized vitamin D3 compared with placebo	4 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Rulla M Tamimi, ScD, Brigham and Women's Hospital; Principal Investigator: Kathy Rexrode, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): March 1, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (Estimate): September 15, 2014

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: mammographic breast density, breast disease, breast tissue
• Additional Relevant MeSH Terms: Skin Diseases; Breast Diseases; Fibrocystic Breast Disease; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2014P000895; R01CA178263 (U.S. NIH Grant/Contract)