Vitamin D and Breast Cancer Biomarkers in Female Patients

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Dietary Supplement: vitamin D; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01224678

CDR0000687263 (Registry Identifier)

CALGB-70806

Details and patient eligibility

About

RATIONALE: Vitamin D may help prevent breast cancer.

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

Full description

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.

Enrollment: 300 patients

Sex: Female

Ages: Under 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

300 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Patients receive oral placebo once daily for 12 months.

Treatment:

Other: placebo

Vitamin D

Experimental group

Description:

Patients receive oral vitamin D (2000 IU) once daily for 12 months.

Treatment:

Dietary Supplement: vitamin D