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

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

Author information

1
Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, MC5483, Palo Alto, CA, 94304, USA.
2
Vincent Coates Foundation Mass Spectrometry Laboratory, Stanford University, Stanford, CA, 94305, USA.
3
Department of Biomedical Informatics, Stanford University School of Medicine, Stanford, CA, 93405, USA.
4
Department of Medicine - Endocrinology, Stanford University School of Medicine, Stanford, CA, 93405, USA.
5
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.
6
Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, MC5483, Palo Alto, CA, 94304, USA. spitteri@stanford.edu.
7
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA. spitteri@stanford.edu.

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:

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

PMID:
29116467
PMCID:
PMC6381934
DOI:
10.1007/s10549-017-4562-4
[Indexed for MEDLINE]
Free PMC Article

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