S0812 High Dose Cholecalciferol in Premenopausal Women at High-Risk for Breast Cancer
Condition: brca1 Mutation Carrier; brca2 Mutation Carrier; Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional

Summary: 
      RATIONALE: Cholecalciferol may prevent breast cancer in premenopausal women.

      PURPOSE: This randomized phase II trial is studying how well cholecalciferol works in
      preventing breast cancer in premenopausal women.
    

Detailed description: 
      OBJECTIVES:

        -  To assess whether mammographic density is reduced in premenopausal women at high risk of
           breast cancer taking high-dose vitamin D3 (oral cholecalciferol 20,000 IU weekly) vs
           placebo for 1 year.

        -  To assess whether proliferation as measured by Ki-67 staining of breast epithelial cells
           is reduced in women receiving these treatments.

        -  To explore the difference in the expression of other biomarkers (including cleaved
           caspase-3 [apoptosis marker], ER, vitamin D receptor [VDR], and 1α-hydroxylase) in
           breast tissue obtained from these women.

        -  To assess whether parathyroid hormone, IGF-1, IGFBP-3, 25(OH)D, and 1,25(OH)D serum
           levels are altered in these women at baseline and at 6 and 12 months.

        -  To explore whether a change in mammographic density correlates with polymorphisms in the
           VDR gene.

        -  To assess other sources of vitamin D (sunlight exposure, diet) in these women using a
           validated questionnaire administered at baseline and at 12 and 24 months.

        -  To collect and bank serum, plasma, and breast tissue from these women before and after a
           1-year intervention with vitamin D for future biomarker analysis.

        -  To assess the toxicity of high-dose cholecalciferol compared to placebo in this setting.

      OUTLINE: This is a multicenter study. Participants are stratified according to baseline serum
      25(OH)D level (< 20 ng/mL vs 20-32 ng/mL or < 50 nmol/L vs 50-80 nmol/L), baseline
      mammographic density (11-50% vs > 50%), and designated biopsy site (yes vs no). Participants
      are randomized to 1 of 2 treatment arms.

        -  Arm I: Participants receive oral cholecalciferol once weekly and oral vitamin D once
           daily. Treatment repeats for 12 months in the absence of evidence of cancer or
           unacceptable toxicity.

        -  Arm II: Participants receive oral placebo once weekly and oral vitamin D once daily.
           Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable
           toxicity.

      Blood samples are collected at baseline and periodically thereafter for biomarkers and
      25(OH)D level. Participants undergo a mammogram at baseline and at 12 months. Participants
      may also undergo random core-needle breast biopsy at baseline and at 12 months.

      Participants complete a questionnaire at baseline and at 12 and 24 months.

      After completion of study therapy, participants are followed up at 1 and 12 months.
    

Intervention name(s): cholecalciferol; placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Given orally; Given orally
Intervention MeSH terms: Cholecalciferol; Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized Phase 2 study
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: breast cancer; ductal breast carcinoma in situ; lobular breast carcinoma in situ; BRCA1 mutation carrier; BRCA2 mutation carrier