Calcium and Vitamin D May Cut Premenopausal Breast Cancer

BOSTON, May 30 -- Calcium and vitamin D intake from food and supplements may confer a moderately lower risk of breast cancer before menopause but not afterward, researchers reported.

Among the premenopausal women, the breast cancer risks for calcium and vitamin D in the highest intake quintile, compared with the lowest, were more than a third lower, reported Jennifer Lin, Ph.D., of Harvard, and colleagues, in the May 28 issue of the Archives of Internal Medicine. The trend for the relationship with vitamin D, however, did not reach statistical significance.

The inverse association for both nutrients, emerging after a mean 10-year follow-up, appeared more pronounced in more aggressive tumors, they added.

Using a food-frequency questionnaire, the investigators evaluated total calcium and vitamin D intake in relation to breast cancer rates in a prospective cohort of 10,578 premenopausal and 20,909 postmenopausal women in the Women's Health Study.

The women, enrolled from 1993 to 1995, were 45 years or older and free of cancer and cardiovascular disease at baseline.

The mean intakes of total calcium and vitamin D in the total cohort were 1,021 mg/d and 353 IU/d, respectively, the researchers reported.

The younger and older women had statistically similar total intakes of both nutrients, with a mean total calcium intake of 965 mg/d versus 1,049 mg/d, and a mean total vitamin D intake of 332 IU/d versus 364 IU/d.

Dairy products accounted for 53% and 39% of the calcium and vitamin D intake, respectively. For vitamin D, 30% came from multivitamin supplements.

During an average 10-year follow-up, 276 premenopausal women (2.6%) and 743 postmenopausal women (3.6 %) had a confirmed diagnosis of incident invasive breast cancer.

Among the premenopausal women, the hazard ratios in the group with the highest relative to the lowest quintile of intake were 0.61 (95% confidence interval, 0.40-0.92) for calcium (P=.04 for trend) and 0.65 (CI, 0.42-1.00) for vitamin D (P=.07 for trend), the researchers reported.

The inverse association with both nutrients was also present for large or poorly differentiated breast tumors among premenopausal women, they said.

By contrast, neither calcium nor vitamin D cut the breast cancer risk among postmenopausal women, and the associations were unchanged by tumor characteristics.

A possible explanation for the differences by menopause status may be related to the joint relationship among calcium, vitamin D, and insulin-like growth factors (IGFs), the researchers suggested.

In-vitro studies have suggested that calcium and vitamin D exert anticarcinogenic effects on breast cancer cells expressing the highest levels of IGF-1 and IGF binding protein 3. Calcium, vitamin D, and IGF binding protein 3 have been shown to interact with one another in promoting growth inhibition in breast cancer cells, the researchers said.

Because circulating levels of these compounds decline with increasing age, the interactions are likely to be stronger in younger women, leading to a greater risk for older women.

However, it is possible that the protective effects of both calcium and vitamin D against postmenopausal breast cancer occur only when intakes of both nutrients are substantially high, they said.

The recent Women's Health Initiative randomized trial also found no reduction in breast cancer among postmenopausal women taking 1,000 mg/d of calcium and 400 IU/d of vitamin D, the researchers said.

"Data from our study suggest that postmenopausal women consuming higher levels of calcium may reduce their breast cancer risk when the level of vitamin D is also high," Dr. Lin said.

It has been suggested, the investigators added, that for older women a minimum of 1,000 IU/d of vitamin D may be necessary to achieve adequate vitamin D concentrations, especially when sunlight exposure is minimal.

Accordingly, the mean 400 IU/d of vitamin D from the subjects in the Women's Health Initiative trial may have been insufficient to reach the hypothesized risk reduction, they said.

The present study, they researchers wrote, had several limitations. Nutrient intake was assessed only at baseline and was subject to measurement error due to random within-person variation.

Furthermore, they noted that they lacked information about Vitamin D intake from sunlight, the major source of vitamin D for most people. "Our lack of information on sun exposure may have attenuated the true association with vitamin D intake," they wrote.

Finally, they said, chance may have played a role because so many subgroup analyses were done.

Further investigation, they concluded, is warranted to study the potential value of calcium and vitamin D intake in reducing the risk of breast cancer.

This study was supported by a grant from the National Cancer Institute, a grant from the National Heart, Lung, and Blood Institute, and career development award from the National Cancer Institute for Dr. Lin.