Vitamin D and breast cancer: evidence for biological and clinical significance

Abstract

Both vitamin D deficiency and breast cancer are common. Laboratory evidence strongly suggests a biological role for vitamin D in normal breast cellular maintenance. Clinically, however, definitive associations between vitamin D and breast cancer risk and outcome have been challenging to decipher. A myriad of epidemiological studies have attempted to connect vitamin D with breast cancer risk, stage at diagnosis and outcome, but results vary. Here, we will closely examine the biologic evidence that supports an association between vitamin D and breast cancer and summarize the epidemiologic and clinical studies in this area. We will discuss ongoing trials and additional research questions that should be addressed in future studies.Vitamin D deficiency is common in general and breast cancer populations and is defined by the Institute of Medicine as a serum 25(OH)D level <20 ng/ml.The Institute of Medicine cut offs defining vitamin D deficiency and insufficiency, based on studies of bone fractures, may not be relevant for breast cancer outcomes. The optimal serum vitamin D level for breast cancer patients is unknown.Low serum level of vitamin D is associated with an increased risk of breast cancer in a recent meta-analysis.Calcitriol, the activated form of vitamin D, can be synthesized within breast cells.Calcitriol binds to intracellular vitamin D receptors and appears to repress proliferation and angiogenesis while inducing differentiation and apoptosis in normal breast cells.Calcitriol or its analogs have been safely combined with various chemotherapy drugs in Phase I and II studies.Combining vitamin D with cytotoxic chemotherapy agents in vitro and in vivo has been shown to increase the activity of some agents used for breast cancer.Vitamin D as a targeted therapy does not appear to be efficacious as a single agent in clinical trials to date.