Vitamin D and Breast Cancer Biomarkers in Female Patients
Vitamin D and Breast Cancer Biomarkers in Female Patients
RATIONALE: Vitamin D may help prevent breast cancer.

 PURPOSE: This randomized clinical trial is studying vitamin D and breast cancer biomarkers in
 female patients.
OBJECTIVES:

 Primary

 -  To evaluate change in mammographic density using the Boyd method after one year of
 vitamin D supplementation compared to placebo in premenopausal women.

 Secondary

 -  To explore changes in the serum biomarker IGF1 in response to one year of vitamin D or
 placebo supplementation in premenopausal women.

 -  To explore changes in cellular proliferation (atypia and Ki67) in response to one year
 of vitamin D or placebo supplementation in premenopausal women.

 -  To explore correlations between change in breast cancer biomarkers (density, IGF1,
 atypia, and Ki67) with each other and with change in vitamin D levels.

 -  To compare methods of mammographic density analysis.

 -  To validate a recently developed sunlight questionnaire.

 OUTLINE: This is a multicenter study. Patients are stratified according to baseline vitamin D
 (sufficient [≥ 30 ng/mL or ≥ 75 mmol/L] vs insufficient [< 30 ng/mL or < 75 mmol/L]) and
 institutional random periareolar fine-needle aspiration (RPFNA) status (performs RPFNA vs
 does not perform RPFNA). Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients receive oral placebo once daily for 12 months.

 -  Arm II: Patients receive oral vitamin D (2000 IU) once daily for 12 months. Tissue and
 blood samples are collected at baseline and at 12 months for laboratory biomarker
 analysis. Patients also complete questionnaires at baseline and at 12 months.
1. Premenopausal women 55 years of age or younger with regular menstrual cycles (at least
 four cycles in the last six months). Women with fewer than 4 menses in the last 6
 months or who have had a hysterectomy with ovaries intact will be considered
 premenopausal if FSH level < 20.

 2. Women with breast density ≥ 25% (scattered fibroglandular densities or greater) are
 eligible.

 3. Prior Treatment

 1. Patients who are currently receiving hormone replacement therapy (estrogen or
 progesterone); or are taking tamoxifen or raloxifene are not eligible. Women who
 have taken these medications must have stopped for at least 4 months prior to
 study entry.

 Topical estrogen (eg, transdermal patches and vaginal estrogens) is allowed.

 2. Patients who are currently using hormonal contraception, should be taking it for
 at least 4 months prior to study entry.

 4. Vitamin D Use

 1. Patients who are taking regular vitamin D supplementation (above 400 IUs daily)
 and refuse or are unable to stop use are not eligible. Women who agree to stop
 will need to do so for at least 6 months prior to registration.

 2. Patients may not start vitamin D supplementation after registration (regardless
 of results of vitamin D testing) but they may continue vitamin D if they are
 already taking 400 IUs daily or less and have been taking vitamin D for at least
 6 months prior to baseline mammogram.

 5. Patients with a history of breast cancer (including DCIS) or ovarian cancer are not
 eligible.

 6. Patients with a history of breast implants or breast reduction are not eligible.

 7. Patients with two or more bone fractures in the past five years are not eligible.

 8. Patients with a diagnosis of osteoporosis with physician recommendation for treatment
 of low bone mass are not eligible.

 9. Patients known to have hyperparathyroid disease or other serious disturbances of
 calcium metabolism requiring intervention in the past 5 years are not eligible.

 10. Patients with a history of kidney stones (unless documented not to have been a calcium
 stone) are not eligible.

 11. Patients participating in a concurrent breast cancer chemoprevention trial are not
 eligible.

 12. Required initial laboratory values - Calcium < 10.5 mg/dL