UC San Diego

Globally, a wide range of epidemiological studies have linked low levels of sunlight, ultraviolet B (UVB) irradiance, or serum 25-hydroxyvitamin D [25(OH)], with increased risk of breast cancer. Three studies of different design were employed to assess the relationship between serum 25(OH)D and breast cancer risk. The first study is an ecological analysis of the relationship between UVB irradiance and age-standardized breast cancer mortality rates worldwide. In the regression model, UVB irradiance was inversely associated with mortality rates (p = 0.04), after controlling for covariates. The overall model was statistically significant (R² = 0.34, p < 0.0001). The second study was a case-control analysis of 600 incident cases of female breast cancer and their matched controls that investigated the inverse association between pre-diagnostic serum levels of 25(OH)D and risk of breast cancer in active-duty U.S. military personnel. Conditional logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, while controlling for race and age. In this study, there was an inverse trend between serum 25(OH)D and odds of breast cancer that did not reach statistical significance. However, in 123 pairs for whom serum was collected 90 days or fewer before case diagnosis, women in the highest quintile of serum 25(OH)D had a 70% lower estimated risk of breast cancer (odds ratio 0.30, 95% confidence interval 0.12-0.74, p <̲ 0.01) compared to those in the lowest quintile. The third study was a pooled analysis of published data from 11 ordinary and nested case-control studies. Data from all 11 studies were combined in order to calculate the pooled odds ratio of the highest vs lowest quintile of 25(OH)D. The pooled odds ratio summarizing the estimated risk in the highest compared to the lowest quintile across all studies was 0.63 (95% confidence interval 0.47, 0.80). These three studies provide compelling evidence that supports a strong inverse relationship between vitamin D status and breast cancer risk. More studies, including randomized controlled trials of higher doses of vitamin D₃ (4,000 IU - 6,000 IU/ day), and serum levels of 25(OH)D (60-80 ng/ml), should be performed without delay