Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

This study has been completed.
Sponsor:
Collaborator:
BTR Group
Information provided by (Responsible Party):
Carol Fabian, MD, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier:
NCT01166763
First received: July 16, 2010
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

The overall goal of this project is to determine if high dose vitamin D3 given to premenopausal women at high risk for development of breast cancer, who initially have insufficient levels of 25-hydroxy vitamin D (<30 ng/ml), will raise 25(OH)D levels above 50 ng/ml. If so, will certain risk biomarkers for development of breast cancer be reliably and favorably modulated?


Condition Intervention
Breast Cancer
Drug: vitamin D3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

Resource links provided by NLM:


Further study details as provided by University of Kansas:

Primary Outcome Measures:
  • Change in Mammographic Breast Density Over Course of Study [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
    Change in the percent of the breast area that is considered to be at higher density on mammogram.


Secondary Outcome Measures:
  • Change in Proliferation (as Assessed by Ki-67) Examined in Breast Epithelial Cells. [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
    Change in percent of cells expressing staining for Ki-67 antibody in breast epithelial cell specimens acquird by RPFNA.

  • OH Vitamin D Levels in Serum [ Time Frame: baseline, 3, and 6 months ] [ Designated as safety issue: No ]
    Assessment of 25(OH)D levels as a measure of circulating vitamin D.


Enrollment: 30
Study Start Date: May 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: high dose vitamin D3 (10,000 IU weekly)
Group/Cohort Label vitamin D3
Drug: vitamin D3
oral capsules, 10,000 IU per week for 6 months
Other Name: Maximum D3

Detailed Description:

Protocol Objectives:

To determine if high dose vitamin D3 given to premenopausal women who initially have insufficient levels of 25-hydroxy vitamin D (<30 ng/ml) will raise 25(OH)D levels above the 50 ng/ml level considered to be required for breast health. If so, will certain risk biomarkers for development of breast cancer be reliably and favorably modulated? The primary endpoint will be a decrease in mammographic breast density (percent area considered at increased density). Change in proliferation (a decrease as assessed by Ki-67) will also be examined. Modulate of expression of genes important in breast cancer risk or reflective of vitamin D's mechanism of action will be studied using quantitative real time polymerase chain reaction (qRT-PCR).

Study Design:

The study is a single-arm open label clinical trial. Women who are high risk for development of breast cancer on the basis of family or personal history will undergo random periareolar fine needle aspiration (RPFNA) to acquire breast cells for assessment of gene expression by qRT-PCR. Women with mammographic density >10% will be eligible for enrollment. All subjects will receive high dose vitamin D3 (3 capsules of 10,000 IU of vitamin D3 every week for 6-8 months). At that time, a repeat RPFNA and mammogram will be performed. Measurement of serum levels of 25(OH)D will be performed at baseline, 3 months, and 6 months.

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be premenopausal women age 55 or younger, and actively menstruating with 4 or more periods per year.
  • Subjects may be using barrier contraceptive, an intrauterine device, a Nuvaring, or similar non-oral contraceptive; or oral contraceptives.
  • Subjects must be at increased risk for breast cancer on the basis of at least one of the following criteria:

    • five-year Gail risk of 3X the average risk of the age group;
    • a first degree relative with breast cancer under the age of 60 or multiple second degree relatives with breast cancer;
    • prior biopsy exhibiting atypical hyperplasia (AH), LCIS, DCIS, RPFNA evidence of hyperplasia with atypia within the last three years;
    • Chest or neck radiation before age 30;
    • Breast density equals or exceeds 50 percent.
  • If previously on a chemoprevention agent or prevention trial, subjects must have completed study participation at least 6 months prior to baseline biomarker assessment.
  • If subject has a history of AH, LCIS, or ER-positive DCIS by diagnostic biopsy, must have been counseled about appropriate standard prevention therapies such as tamoxifen and is either not eligible or is not interested in standard prevention therapies. Women with DCIS must have had appropriate local therapy (lumpectomy plus radiation or mastectomy).
  • Subject must have had a mammogram performed at the University of Kansas Breast Imaging Center with estimated visual breast density of greater than 10 percent.
  • Subject must have had within six months prior to entering the study, an RPFNA during the follicular portion (day 1-10) of the menstrual cycle with material for cytomorphology, Ki-67 and qRT-PCR; in addition to serum obtained and banked.
  • Subjects must have 25(OH)D level < 30 ng/ml as measured within 8 weeks of starting intervention. Subjects may have been identified as having low vitamin D levels through participation in HSC 11313, Osteopenia/Osteoporosis in Pre-menopausal Women at High Risk for Development of Breast Cancer, but low level must be confirmed within 8 weeks prior to starting study agent Subject must be willing to continue the same hormonal milieu present at baseline throughout trial.
  • Subjects must be willing to undergo measurement of height, weight, and BMI at initiation of intervention.
  • Subjects must have participated in HSC 11313, and have had a DEXA scan for bone density and body fat analysis on the GE Lunar Prodigy Advance research unit in the Breast Cancer Survivorship Center.
  • Subjects must be willing to sign an informed consent for the entire study and separate consent for repeat RPFNA.

Exclusion Criteria:

  • Women that have had a metastatic malignancy of any kind.
  • Women that have had prior invasive breast cancer If subject has had a DCIS, at least two months must have elapsed from surgery and/or radiation therapy to the involved breast. Only the contra-lateral (uninvolved breast) will be studied by FNA. The subject may not have had any radiation therapy to the contra-lateral breast to be studied.
  • Women who are pregnant or nursing.
  • Women who have taken a SERM, aromatase inhibitor or participated in a chemoprevention or other investigational drug study within six months prior to baseline FNA.
  • Women who have used fertility drugs within six months prior to baseline aspiration.
  • Women with a history of sarcoidosis, hypercalcemia, hyperparathyroidism, or renal stones.
  • Women who are receiving treatment for rheumatoid arthritis or other connective tissue diseases.
  • Women who have an elevated blood calcium level at baseline; defined as any elevation above the institutional normal range.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01166763

Locations
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Sponsors and Collaborators
Carol Fabian, MD
BTR Group
Investigators
Principal Investigator: Carol Fabian, MD University of Kansas
  More Information

No publications provided

Responsible Party: Carol Fabian, MD, Professor, Director Breast Cancer Prevention Unit, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT01166763     History of Changes
Other Study ID Numbers: 11657
Study First Received: July 16, 2010
Results First Received: January 27, 2014
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kansas:
breast atypia
high risk for breast cancer
random periareolar fine needle aspiration
RPFNA
breast epithelial hyperplasia
ki-67
chemoprevention
vitamin D3
Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Breast Neoplasms
Pharmacologic Actions
Hyperplasia
high risk for development of breast cancer
Neoplasms
Neoplasms by Site
Pathologic Processes
Antirheumatic Agents
Breast Diseases

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Molecular Mechanisms of Pharmacological Action
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on October 01, 2014