Breast cancer survival is enhanced by higher serum levels of vitamin D

Breast cancer survival is linked to higher serum levels of 25-hydroxyvitamin D [25(OH)D] according to evidence presented in a meta-analysis just published in the journal Anti-Cancer Research. The authors set out to...

"...determine whether higher serum 25-hydroxyvitamin D [25(OH)D] at diagnosis is associated with longer survival of patients with breast cancer."

They conducted a meta-analysis of five studies examining the relationship between 25(OH)D and mortality from breast cancer that met their rigorous inclusion criteria from among 77 studies. The data showed a marked association between breast cancer survival and serum vitamin D levels:

"For breast cancer, serum 25(OH)D had a strong preventive effect against mortality. Of the five studies performed on the relationship between serum 25(OH)D and breast cancer mortality, three found a statistically significant reduction in mortality with increasing 25(OH)D concentrations. One study found a beneficial effect that did not reach statistical significance, while the fifth study found a beneficial effect in the age-adjusted but not multivariate analysis. Individuals with higher serum concentrations of 25(OH)D had substantially lower fatality rates. Of the five studies, three found that serum 25(OH)D in the highest quantile was associated with substantially lower fatality rates than serum 25(OH)D in the lowest quantile, and two found a trend in the same direction..."

In brief..."Higher serum 25(OH)D concentrations were associated with lower fatality rates in patients with breast cancer. Patients with the highest concentration of 25(OH)D had approximately half the fatality rate compared to those with the lowest concentration."Regarding possible mechanisms:

"Laboratory studies have demonstrated anticancer effects of vitamin D metabolites on three critical phases in the development of breast tumors: differentiation, apoptosis, and angiogenesis. It is possible that the association of serum 25(OH)D with survival depends on maintaining differentiation, promoting apoptosis, and inhibiting angiogenesis. These are all known function of vitamin D metabolites...On the other hand, the results of the present study could have resulted from reverse causation. It is possible that in the more serious cases, the serum 25(OH)D concentration was reduced and these were also the cases that resulted in death early in their natural history. If that were so, serum 25(OH)D could be a biomarker for severity of cancer, rather than a factor that caused longer survival. This possibility could be ruled-out by performance of a clinical trial. There is one clinical trial of a reasonable dose of vitamin D (1000 IU) with calcium that showed a 77% reduction in incidence of all combined invasive cancer, including breast cancer. A clinical trial should be performed using the upper-level dose recommended by the National Academy of Sciences, which is 10,000 IU/day of vitamin D3."

However...

"In the meantime, no laboratory study to our knowledge has shown that tumors can reduce the serum 25(OH)D concentration. The death rate from cancer is also much lower in areas of the US with high solar UVB irradiance than those with lower irradiance, which cannot be accounted for by reverse causation. There is a similar association on a worldwide basis."

 Of great value are statements by senior author Cedric F. Garland, DrPH from the Department of Family and Preventive Medicine at the University of California, San Diego quoted by Medscape Medical News:

"Vitamin D makes cells stick together, particularly breast epithelial cells, by producing upregulation of the synthesis of E-cadherin. If the vitamin D level gets low, the cells of the breast epithelium don't adhere to each other, and when a cell is not tightly adherent to its neighbors, its stem cells undergo rapid mitosis. The cells that reproduce the fastest can produce a cancerous clone, which can ultimately penetrate the basal membrane. If the vitamin D deficiency continues, those cells will get out into the lymphatics, metastasize to the brain, bone, and lungs, and kill the patient."

Moreover...

"With a lot of vitamin D, the cells are self-adherent and never evolve into a cancer," he noted. "If it's late in the history and they have evolved into a cancer, it will be a well-differentiated cancer. Those are not as aggressive as the poorly differentiated cells that will eventually break through a blood vessel and kill people. As long as the cells have a vitamin D receptor intact — and most cells do because it's a very robust receptor — the vitamin D will make the tumor stop growing. It will freeze it in its track," he said.Doctors should measure vitamin D levels in their breast cancer patients. If they are deficient, they should be started immediately on 40,000 IU of vitamin D daily to get it up to 40 to 60 ng/mL, Dr. Garland advised."

 The authors of the meta-analysis  conclude with a comment of significant practical significance:

"These studies suggest it might be prudent for patients with breast cancer to have their serum 25(OH)D measured and repleted to concentrations in the normal range (30-80 ng/ml) pending the performance of a randomized controlled clinical trial. Numerous studies of the safety of vitamin D3 are available that would make such a strategy worth considering."