br A meta analysis of data taken from
A meta-analysis of data taken from the Cancer Genome Atlas (TCGA) cohort (Project Id: TCGA-Breast Cancer) (n = 780 patients) (https:// portal.gdc.cancer.gov/projects/TCGA-BC) demonstrated that over five
years, patients with clinically-diagnosed Puromycin receptor negative breast cancer had similar survival rates regardless of CYP24A1 ex-pression. However, patients with estrogen receptor positive breast cancer with higher-than-median CYP24A1 levels had significantly better survival rates over 5 years than patients with low levels of CYP24A1 (Fig. 4). Another meta-analysis of vitamin D supplementation in breast cancer patients that considered estrogen receptor positive/ negative and progesterone receptor positive/negative subtypes found that although vitamin D supplementation was associated with de-creased recurrence rates in patients with estrogen receptor positive cancer, there was no correlation between vitamin D supplementation and hazard ratios in patients with estrogen receptor negative cancer . These results were maintained regardless of progesterone receptor status, suggesting that estrogen receptor status is a better outcome marker of vitamin D supplementation eﬃcacy than progesterone re-ceptor. Taken together, these results suggest that estrogen receptor expression could be of clinical importance in the eﬃcacy of vitamin D supplementation in breast cancer patients Fig. 5.
Although connections between improved breast cancer prognoses and high vitamin D serum levels have been well-established, there is no consensus on the eﬃcacy of vitamin D supplementation in the treat-ment of breast cancer. Studies examining breast cancer prognosis and vitamin D serum levels could be improved by considering the breast cancer molecular subtypes, particularly the estrogen receptor status, of the patients involved. 24R,25(OH)2D3, an understudied vitamin D3 metabolite, may have potential as a less-calcemic vitamin D3 metabo-lite with tumor modulating properties. Further research is needed to understand the connections between estrogen receptor status and the anti-tumorigenicity of vitamin D supplements, and the parallels be-tween membrane mediated estrogen signaling through ERα36 and 24R,25(OH)2D3 may provide insight into this connection.
Services in support of the research project were provided by the VCU Massey Cancer Mouse Models Core, supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
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