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Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

55 Years
Not Enrolling
Breast Cancer

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Trial Information

Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

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.

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

- 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

- 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

- 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

- Women who are receiving treatment for rheumatoid arthritis or other connective tissue

- Women who have an elevated blood calcium level at baseline; defined as any elevation
above the institutional normal range.

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Mammographic breast density

Outcome Description:

Assessed as area of mammogram at increased density

Outcome Time Frame:

baseline and 6 months

Safety Issue:


Principal Investigator

Carol Fabian, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kansas


United States: Food and Drug Administration

Study ID:




Start Date:

May 2009

Completion Date:

June 2011

Related Keywords:

  • Breast Cancer
  • breast atypia
  • high risk for breast cancer
  • random periareolar fine needle aspiration
  • 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
  • Breast Neoplasms



University of Kansas Medical Center Kansas City, Kansas  66160-7353