Pamela J. Goodwin, MD, MSc
Editor’s Note: Evidence is accumulating that suggests a link between low vitamin D levels and poor prognosis in breast cancer. However, while studies demonstrate an association between the two, clinicians are faced with the task of addressing the issue with patients and answering questions about vitamin D supplementation. Selecting an optimal dose for supplementation can be especially challenging because little correlation exists between the amount of vitamin D consumed and blood levels. At the 2009 Annual Meeting of the American Society of Clinical Oncology, held in Orlando, Florida, from May 29 to June 2, 2009, additional studies regarding vitamin D and breast cancer were presented. While at the ASCO meeting, Medscape Oncology contributor Emma Hitt, PhD, discussed the role of vitamin D in breast cancer and recent findings on the topic with Pamela J. Goodwin, MD, a Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, in Toronto, Ontario, Canada.
Medscape: You recently reported the findings of a prospective study in the Journal of Clinical Oncology showing that low vitamin D levels were associated with poor outcomes in breast cancer. Can you describe those findings and their clinical significance?
Dr. Goodwin: We evaluated a cohort of 512 women who had been diagnosed with breast cancer between 1989 and 1996, and at the time of diagnosis, we measured their vitamin D levels — after surgery but before they started treatment. We then followed them for 11.6 years; during that time, 116 women had distant recurrences, and 106 women died. We found that women with low vitamin D levels tended to be more obese and to have higher-grade tumors.
They were also at a greater risk for both distant recurrence and death; low levels of vitamin D were associated with an increased risk for distant recurrence, with a hazard ratio of 1.94 (ie, an almost doubled risk). Decreased survival was also associated with the lowest vitamin D levels, with a hazard ratio of 1.73. For the most part, these effects remained significant upon multivariate analyses, even after adjusting for a large number of factors.
What we found, though, was an association, not a cause-and-effect relationship (ie, we are unable to say that the low vitamin D caused the poor outcomes). Vitamin D levels are associated with a large number of factors, including diet, physical activity, sun exposure, and general overall health. Although we tried to control for as many of those as we could, in this observational setting it could not be definitively concluded that these outcomes resulted from low levels of vitamin D.
Medscape: What are the potential mechanisms that may explain this association?
Dr. Goodwin: We measured 25-hydroxy vitamin D, the predominant circulating form of vitamin D in the blood, which is converted in breast cancer tissue to the active form, 1,25-dihydroxy vitamin D. This then binds to vitamin D receptors present on breast cancer cells, and the vitamin D receptors then translocate to the nucleus, bind to vitamin D response elements in genes, and regulate the transcription of over 200 genes that are responsible for proliferation, differentiation, apoptosis, and adhesion; thus, the biology for an effect of vitamin D in breast cancer is quite strong. Several studies at ASCO this year addressed the association between vitamin D and breast cancer.