Breast Cancer death 1.8 X more likely if poor Vitamin D Receptor – April 2019

Vitamin D receptor expression in invasive breast tumors and breast cancer survival - July 2019

Breast Cancer Research volume 21, Article number: 84 (2019)
Linnea Huss, Salma Tunå Butt, Signe Borgquist, Karin Elebro, Malte Sandsveden, Ann Rosendahl & Jonas Manjer

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Background
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.

Methods
VDR 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.

Results
We 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.

Conclusions
This 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.

Vitamin D and Breast Cancer. Studies on Incidence and Survival - dissertation

Huss, Linnea LU PHD Dissertation
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Breast Cancer Survival if have low levels of Vitamin D at time of diagnosis

Note: Increase survival if increase Vitamin D and/or increase VDR activation

Previous research has suggested beneficial effects of vitamin D on both breast cancer risk and prognosis. The overall aim of this research project was to investigate associations between vitamin D and breast cancer. The population-based prospective cohort, the Malmö Diet and Cancer Study, recruited 17,034 women in the first half of the 1990s. Studies in in the current thesis are based on blood samples collected at baseline, analyzed for levels of vitamin D, parathyroid hormone (PTH), calcium and later also used for genetic sequencing. Breast tumors that developed in women within the cohort were included in a tissue microarray and analyzed for expression of the vitamin D receptor (VDR).
Specific aims were to investigate:

• I. Serum levels of vitamin D, PTH and calcium in relation to breast cancer survival, i.e. mortality among women diagnosed with breast cancer.
• II. Vitamin D-related single nucleotide polymorphisms (SNPs) and breast cancer risk.
• III. Expression of VDR in association with breast cancer mortality.
• IV. Levels of vitamin D in relation to expression of VDR in subsequent breast tumors.

Results and conclusions:

• I. Compared to intermediate levels of vitamin D, low levels and high levels were associated with a poor survival, i.e. high risk of death related to breast cancer. No association was found between PTH and breast cancer mortality. Relatively high serum calcium levels were associated with relatively low breast cancer mortality.
• II. SNPs associated with levels of vitamin D did not affect breast cancer risk. One SNP, related to the vitamin D binding protein, was associated with breast cancer risk.
• III. VDR expression was associated with a favorable breast cancer prognosis.
• IV. There were indications that vitamin D levels were associated with VDR expression in a subsequent breast tumor.

The association between low vitamin D levels and high breast cancer mortality may be mediated through development of a VDR-negative tumor. There was no evidence to suggest an additional beneficiary effect of vitamin D levels higher than intermediate levels.