Vitamin D supplementation decreases serum 27-hydroxycholesterol in a pilot breast cancer trial

Breast Cancer Res Treat. 2018 Feb;167(3):797-802. doi: 10.1007/s10549-017-4562-4. Epub 2017 Nov 7.


Purpose: 27-hydroxycholesterol (27HC), an endogenous selective estrogen receptor modulator (SERM), drives the growth of estrogen receptor-positive (ER+) breast cancer. 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, is known to inhibit expression of CYP27B1, which is very similar in structure and function to CYP27A1, the synthesizing enzyme of 27HC. Therefore, we hypothesized that 1,25(OH)2D may also inhibit expression of CYP27A1, thereby reducing 27HC concentrations in the blood and tissues that express CYP27A1, including breast cancer tissue.

Methods: 27HC, 25-hydroxyvitamin D (25OHD), and 1,25(OH)2D were measured in sera from 29 breast cancer patients before and after supplementation with low-dose (400 IU/day) or high-dose (10,000 IU/day) vitamin D in the interval between biopsy and surgery.

Results: A significant increase (p = 4.3E-5) in 25OHD and a decrease (p = 1.7E-1) in 27HC was observed in high-dose versus low-dose vitamin D subjects. Excluding two statistical outliers, 25OHD and 27HC levels were inversely correlated (p = 7.0E-3).

Conclusions: Vitamin D supplementation can decrease circulating 27HC of breast cancer patients, likely by CYP27A1 inhibition. This suggests a new and additional modality by which vitamin D can inhibit ER+ breast cancer growth, though a larger study is needed for verification.

Keywords: 27-hydroxycholesterol; CYP27A1; Calcitriol; ER+ breast cancer; Vitamin D.

Publication types

  • Clinical Trial

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Biopsy
  • Breast Neoplasms / blood
  • Breast Neoplasms / diet therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cell Line, Tumor
  • Cholestanetriol 26-Monooxygenase / antagonists & inhibitors
  • Cholestanetriol 26-Monooxygenase / genetics*
  • Dietary Supplements
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hydroxycholesterols / blood*
  • Receptors, Estrogen / genetics
  • Selective Estrogen Receptor Modulators / administration & dosage
  • Vitamin D / administration & dosage*


  • Hydroxycholesterols
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • Vitamin D
  • 27-hydroxycholesterol
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human