Abstract

BackgroundVitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis.MethodsVDR expression was evaluated in a tissue microarray of 718 invasive breast tumors. Covariation between VDR expression and established prognostic factors for breast cancer was analyzed, as well as associations between VDR expression and breast cancer mortality.ResultsWe found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67. In addition, both intranuclear and cytoplasmic VDR expression were associated with a low risk of breast cancer mortality, hazard ratios 0.56 (95% CI 0.34–0.91) and 0.59 (0.30–1.16) respectively.ConclusionsThis study found that high expression of VDR in invasive breast tumors is associated with favorable prognostic factors and a low risk of breast cancer death. Hence, a high VDR expression is a positive prognostic factor.

Highlights

  • Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer

  • When cancer in situ cells were noted in the same core as invasive tumor cells, in situ cells were differently stained compared to invasive cells

  • Due to difficulties in distinguishing vitamin D receptor (VDR) expression between nuclear membrane and cellular membrane, there was a high percentage of discordance between the first and second rounds of scoring at these compartments (14.1% of nuclear membrane fraction and 30.1% of cellular membrane fraction)

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Summary

Introduction

Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis

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