No Breast Cancer Risk Reduction Seen With Calcium, Vitamin D


ATLANTA — Calcium plus vitamin D supplementation in postmenopausal women does not appear to reduce their risk of breast cancer, according to results from a Women's Health Initiative randomized trial presented at the annual meeting of the American Society of Clinical Oncology.

After a median of 7 years, women who received 1,000 mg of calcium carbonate plus 400 IU of vitamin D3 were no less likely to develop breast cancer than were women who received placebo. In the study, Dr. Rowan T. Chlebowski and his colleagues randomized 36,282 women aged 50–79 years with no prior breast cancer who were already enrolled in the WHI diet or hormone trials to receive calcium plus vitamin D or placebo. Supplements were provided by GlaxoSmithKline.

In her discussion of the study, Dr. Carol Fabian suggested that several variables could have contributed to the lack of effect observed in the study. First, the mean calcium intake at baseline was 1,165 mg/day in both arms, already approaching the recommended optimal intake.

Second, women in either arm could, on their own, use supplements of up to 1,000 mg of calcium and 1,000 IU of vitamin D per day. During the fifth year of the trial, nonprotocol supplement use on average totaled 200 mg of calcium and 400 IU of vitamin D—an amount of vitamin D equivalent to the study dose, noted Dr. Chlebowski, a professor of medicine at the University of California, Los Angeles, in his presentation. This reduced the difference in vitamin D intake between the experimental and control arms.

Dr. Fabian, a professor of medicine at the University of Kansas Medical Center in Kansas City, said that recent studies indicate that the amount of vitamin D needed to see a benefit for breast cancer reduction may be quite high, about 3,000 IU per day. This is significantly higher than the study dose of 400 IU per day.

“I would like to suggest, although we don't know, that the intervention did not provide nearly enough vitamin D,” Dr. Fabian said. She recommended that women strive to get 15–20 minutes of sun per day or take 1,000–2,000 IU vitamin D3 per day. “If this sounds like a high level to you, I will point out … a number of vitamin D experts who think that the current recommendations that we see for vitamin D are way too low, and we must increase the levels to at least 1,000 units of vitamin D per day.”

Whereas calcium intake at baseline was already high, women entering the study had fairly low vitamin D levels at baseline; 85% of women had a serum 25-hydroxyvitamin D level below 30 ng/mL, suggesting vitamin D insufficiency. Among the 19,115 women not using vitamin D supplements at baseline, those in the calcium plus vitamin D group had a significant 18% reduction in breast cancer risk. Dr. Fabian also said that by enrolling postmenopausal women, the trial could have started supplementation too late in the precancerous process.

The primary end point of the trial, the incidence of hip fracture, was not significantly different between arms (N. Engl. J. Med. 2006;354:669–83), nor was the incidence of colorectal cancer (N. Engl. J. Med. 2006;354:684–96). As previously reported, there was a significant 17% increased incidence of kidney stones with calcium plus vitamin D.

The current analysis found no relationship between baseline serum 25-hydroxyvitamin D levels and arthritis incidence. Moreover, after 2 years, calcium plus vitamin D had no effect on joint pain or swelling. Estrogen use did appear to significantly reduce joint pain. After 3 years, the incidence of joint pain in women taking estrogen was 70.6%, compared with 77.2% in those not taking estrogen.

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