Vitamin D and Mammographic Breast Density

OBJECTIVES

Primary:

• to determine whether adding oral supplementation with vitamin D3 (cholecalciferol) at doses of 1,000, 2,000 and 3,000 IU/d to baseline total vitamin D intake over a period of 12 months reduces mammographic breast density among premenopausal women at moderate to high risk of breast cancer who reside in the Quebec City area, Canada.

Secondary:

• to assess the net increase in 25(OH)D levels resulting from this vitamin D3 supplementation;
• to document the compliance with, and safety of, supplementation with tested doses of vitamin D3 over one year.

OUTLINE This study is a double-blind, placebo-controlled, randomized trial among premenopausal women who live in the Quebec City area and have ≥ 20% breast density at baseline.

The intervention consists of the addition, over baseline total vitamin D intake from food and supplements, of three different doses of vitamin D3 (1000, 2000 or 3000 IU/day) for a period of 12 months. There are four arms in the trial:

• Arm 1: 1,000 IU vitamin D3/d (1 tablet vitamin D 1000 IU + 2 tablets placebo);
• Arm 2: 2,000 IU vitamin D3/d (2 tablets vitamin D 1000 IU + 1 tablet placebo);
• Arm 3: 3,000 IU vitamin D3/d (3 tablets vitamin D 1000 IU);
• Arm 4: placebo (3 tablets placebo/d).

Vitamin D tablets (1000 IU tablets) and the placebo tablets are undistinguishable in size, shape, color and taste, and are manufactured by the same company.

Inclusion criteria

• be premenopausal at baseline;
• have breast density of at least 20% at baseline;
• have normal baseline serum calcium (2,12-2,60 mmol/L) and serum creatinine (45-85 μmol/L);
• agree to have her mammogram at 12 months of follow-up at the same mammography clinic (same site) as the one where the mammogram at recruitment was done.

Exclusion criteria

• taking > 400 IU/day of supplemental vitamin D and refusing to reduce (≤ 400 IU/day) or cease such intake;
• taking > 600 mg/day of supplemental calcium and refusing to reduce (≤ 600 mg/day) or cease such intake;
• have contra-indications for use of vitamin D supplementation (hypersensitivity to vitamin D or its analogues; a history of renal calculi or hypercalcemia, hypervitaminosis D);
• taking medication suspected to interact with vitamin D: frequent use of antacids containing magnesium or aluminium; regular use of anticonvulsants (phenytoin, phenobarbital), digoxin, cholestyramine, colestipol, orlistat, mineral oil;
• have a personal history of breast cancer;
• have a personal history of cancer other than non-melanoma skin cancer within 5 last years;
• have had breast reduction or augmentation including breast implantation (or planning to undergo such surgery during the trial);
• be pregnant or planning a pregnancy in the next year.