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Breast Cancer Research and Treatment

, Volume 167, Issue 3, pp 797–802 | Cite as

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

  • Catherine C. Going
  • Ludmila Alexandrova
  • Kenneth Lau
  • Christine Y. Yeh
  • David Feldman
  • Sharon J. Pitteri
Brief Report

Abstract

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

Vitamin D Calcitriol 27-hydroxycholesterol ER+ breast cancer CYP27A1 

Abbreviations

1,25(OH)2D

1,25-Dihydroxyvitamin D

25OHD

25-Hydroxyvitamin D

27HC

27-Hydroxycholesterol

ER+

Estrogen receptor-positive

LC–MS/MS

Liquid chromatography tandem mass spectrometry

SERM

Selective estrogen receptor modulator

SRM

Selected reaction monitoring

Notes

Acknowledgements

The authors would like to acknowledge funding for this project from the Vincent Coates Foundation Mass Spectrometry Laboratory in the form of a SUMS Seed Grant. We are grateful to Dr. Melinda Telli, Dr. Kristin Jensen, and members of the Feldman Lab that carried out this trial for their generous access to serum specimens of many of the subjects.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2017_4562_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOCX 24 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Radiology, Canary Center at Stanford for Cancer Early DetectionStanford University School of MedicinePalo AltoUSA
  2. 2.Vincent Coates Foundation Mass Spectrometry LaboratoryStanford UniversityStanfordUSA
  3. 3.Department of Biomedical InformaticsStanford University School of MedicineStanfordUSA
  4. 4.Department of Medicine – EndocrinologyStanford University School of MedicineStanfordUSA
  5. 5.Stanford Cancer InstituteStanford University School of MedicineStanfordUSA

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