Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer prevention and treatment. Preclinical studies support various antitumor effects of vitamin D in breast cancer. Numerous observational studies have reported an inverse association between vitamin D status, including circulating 25-hydroxyvitamin D (25(OH)D) levels, and breast cancer risk. The relationship between vitamin D and mammographic density, a strong predictor of breast cancer risk, remains unclear. Studies analyzing the link between genetic polymorphisms in vitamin D pathway genes and breast cancer incidence and prognosis have yielded inconsistent results. Vitamin D deficiency among breast cancer patients has been associated with poorer clinical outcomes and increased mortality. Despite a number of clinical trials of vitamin D supplementation, the efficacy, optimal dosage of vitamin D, and target blood level of 25(OH)D for breast cancer prevention have yet to be determined. Even with substantial literature on vitamin D and breast cancer, future studies need to focus on gaining a better understanding of the biologic effects of vitamin D in breast tissue. Despite compelling data from experimental and observational studies, there is still insufficient data from clinical trials to make recommendations for vitamin D supplementation for breast cancer prevention or treatment. 1. Introduction Breast cancer confers significant morbidity and mortality among women in the United States. Due to the magnitude of this disease, considerable research effort has been directed toward identifying breast cancer risk factors to target for prevention. However, relatively few modifiable lifestyle and environmental factors have been associated with reduced breast cancer risk. Chemoprevention refers to altering the carcinogenesis process with a drug intervention. The selective estrogen receptor modulators (SERMs), tamoxifen [1] and raloxifene [2], and aromatase inhibitor (AI), exemestane [3], have been shown to reduce breast cancer incidence. These antiestrogens are the only drugs that have been approved by the USA Food and Drug Administration for breast cancer prevention in high-risk population; however, uptake has been poor in the prevention setting. Due to serious toxicities associated with SERMs, namely, endometrial cancer and thromboembolic disease, and chronic toxicities of AIs, such as hot flashes, arthralgias, and osteoporosis, they have not gained widespread acceptance in the primary prevention setting. In addition, these antiestrogens do not lower the incidence of
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