LONDON -- There's more evidence that vitamin D is protective against breast cancer progression, but the relationship remains less than definitive, researchers here said.
LONDON, Oct. 17 -- There's more evidence suggesting that vitamin D may be protective against breast cancer progression, but the relationship remains less than definitive, researchers here said.
Serum levels of 25-hydroxyvitamin D, the major circulating form of vitamin D, were significantly higher in patients with locally advanced or metastatic breast cancer compared with those who had early-stage disease, according to a study reported online in the Journal of Clinical Pathology.
"Whatever the cause for the change in vitamin D levels, it can potentially have a marked effect on gene transcription and therefore on cellular phenotype," wrote Carlo Palmieri, M.B., B.S., Ph.D., of Imperial College London, and colleagues. "Lower serum vitamin D levels might therefore have some causative role in the progression from early-stage to advanced disease."
Patients with early-stage breast cancer had a "markedly higher" average circulating 25-hydroxyvitamin D concentration of 57 nmol/l (95% confidence interval 52.7 to 60.5 nmol/l) compared with 46.0 nmol/l (95% CI 40.9 to 51.8 nmol/l) in patients with locally advanced or metastatic breast cancer.
The difference was significant (P=0.048), though vitamin D levels ranged widely in both groups (15.0 to 184.0 nmol/l early stage versus 16 to 146 nmol/l later stage).
The study "lends weight" to previous laboratory and epidemiological studies that have suggested vitamin D may deter the pathogenesis of breast cancer, the authors said.
In vitro studies showed that 1,25-dihydroxyvitamin D inhibits the proliferation of breast cancer cell lines, promotes differentiation and induces apoptosis. Population-based studies showed that lower latitudes, with more vitamin-D producing sunlight, have lower breast cancer incidences while vitamin D sufficiency has been linked to lower risk of developing breast cancer.
The study included 279 Caucasian women with invasive breast cancer. Of these, 204 women had early-stage breast cancer (stage I or II) and 75 had locally advanced or metastatic disease (stage III or IV).
Using blood samples from clinic visits, the investigators measured circulating levels of 25-hydroxyvitamin D, parathyroid hormone, and calcium, since all three function together. Vitamin D enhances absorption of calcium and parathyroid hormone acts to synthesize an active form of vitamin D.
Patients with renal impairment, receiving bisphosphonate therapy, or on epilepsy drugs were excluded. Normal laboratory reference ranges were 15 to 100 nmol/l for vitamin D, 1.06 to 5.3 pmol/l for parathyroid hormone, and 2.15 to 2.65 mmol/l for corrected calcium.
Parathyroid hormone levels were "considerably lower" in patients with early-stage breast cancer compared with patients who had advanced breast cancer. The mean was significantly lower for the early-stage group (3.91 pmol/l, 95% CI 3.7 to 4.2 pmol/l) compared to the advanced-stage group (5.06 pmol/l, 95% CI 4.4 to 5.8 pmol/l, P=0.001). Parathyroid hormone levels ranged from 1.2 to 11.3 pmol/l for the early-stage group and from 1.05 to 14.1 pmol/l in the advanced-stage group.
This difference was "presumably due to the lower vitamin D level, resulting in a lower serum calcium and therefore a rise in serum [parathyroid hormone]," the researchers suggested.
There was no significant difference between the early- and advanced-stage groups in calcium levels (2.34 mmol/l versus 2.34 mmol/l, P=0.74). The raised PTH level could account for the lack of any difference in serum calcium between these two groups, Dr. Palmieri and colleagues noted.
However, they acknowledged that the study does not explain the cause and mechanisms underlying the differences in vitamin D regulation in these two groups. Nor does it comment on whether monitoring or maintaining high circulating vitamin D levels in patients diagnosed with breast cancer would be of benefit.
It remains unclear whether low circulating vitamin D is "causative for the advanced disease or is a direct consequence of the advanced disease as a result of cancer-related reduced dietary intake or altered synthesis in the skin due to reduced sun exposure," they wrote.