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Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

Primary Purpose

Breast Cancer

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
vitamin D3
Sponsored by
Carol Fabian, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer focused on measuring 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

Eligibility Criteria

undefined - 55 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Kansas Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

high dose vitamin D3 (10,000 IU weekly)

Arm Description

Group/Cohort Label vitamin D3

Outcomes

Primary Outcome Measures

Change in Mammographic Breast Density Over Course of Study
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.
Change in percent of cells expressing staining for Ki-67 antibody in breast epithelial cell specimens acquird by Random Periareolar Fine Needle Aspiration.
OH Vitamin D Levels in Serum
Assessment of 25(OH)D levels as a measure of circulating vitamin D.

Full Information

First Posted
July 16, 2010
Last Updated
June 16, 2016
Sponsor
Carol Fabian, MD
Collaborators
BTR Group
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1. Study Identification

Unique Protocol Identification Number
NCT01166763
Brief Title
Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D
Official Title
Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Carol Fabian, MD
Collaborators
BTR Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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?
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
high dose vitamin D3 (10,000 IU weekly)
Arm Type
Experimental
Arm Description
Group/Cohort Label vitamin D3
Intervention Type
Drug
Intervention Name(s)
vitamin D3
Other Intervention Name(s)
Maximum D3
Intervention Description
oral capsules, 10,000 IU per week for 6 months
Primary Outcome Measure Information:
Title
Change in Mammographic Breast Density Over Course of Study
Description
Change in the percent of the breast area that is considered to be at higher density on mammogram.
Time Frame
baseline and 6 months
Secondary Outcome Measure Information:
Title
Change in Proliferation (as Assessed by Ki-67) Examined in Breast Epithelial Cells.
Description
Change in percent of cells expressing staining for Ki-67 antibody in breast epithelial cell specimens acquird by Random Periareolar Fine Needle Aspiration.
Time Frame
baseline and 6 months
Title
OH Vitamin D Levels in Serum
Description
Assessment of 25(OH)D levels as a measure of circulating vitamin D.
Time Frame
baseline and 6 months

10. Eligibility

Sex
Female
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carol Fabian, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Global results only will be published.

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Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

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