WHI Calcium/Vit D Trial:
WHI Calcium/Vit D Trial:
ATLANTA Attendees at the 42nd Annual Meeting of the American Society of Clinical Oncology were eager to learn whether calcium and vitamin D supplementation has beneficial effects on breast cancer, mammograms, and arthralgias. They heard from Women's Health Initiative (WHI) researchers that the dietary intervention had little effect on any of the primary endpoints (abstract LBA6).
The attendees also heard experts contend that the WHI outcome may have been partly attributable to weaknesses in the design of this enormous study.
The discussant for the paper, Carole Fabian, MD, of the University of Kansas Medical Center, Kansas City (see Vantage Point), suggested the design suffered from being "too little, too late," meaning the vitamin D dose was probably too low and the population studied may have been too old to benefit from the intervention. "We should start with phase II biomarker-based studies to demonstrate proof of principle before embarking on such large trials," Dr. Fabian said.
WHI lead investigator Rowan T. Chlebowski, MD, of the Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, said that the 38,000 patient, 7-year study showed no significant effects of calcium and vitamin D supplementation on any of the three study endpoints but did produce an intriguing suggestion that cancers were smaller in the women who took the supplements.
"Calcium and vitamin D intake have been associated with reduced breast cancer risk and reduced mammographic breast density in observation studies. However, randomized trial evidence of calcium/vitamin D supplementation for breast cancer primary prevention is lacking. In addition, vitamin D deficiency is associated with increased arthralgias/myalgias in breast cancer patients, suggesting an estrogen/vitamin D interaction," Dr. Chlebowski said.
The WHI researchers set out to determine whether daily supplementation with calcium and vitamin D would lower breast cancer risk. They randomized postmenopausal women without prior breast cancer from 40 clinical centers to a daily dose of 1,000 mg of elemental calcium as calcium carbonate and 400 IU of vitamin D (n = 16,936) or to matching placebo (n = 16,815).
More than half (54%) of these study subjects also had been randomized 1 year previously to a study of hormone replacement therapy (HRT) vs placebo. The primary study endpoint of that study was hip fracture incidence. The secondary endpoints were colorectal cancer and breast cancer incidence.