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The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer.

Publication ,  Journal Article
McDonnell, DP; Chang, C-Y; Nelson, ER
Published in: Climacteric
December 2014

Despite increased survivorship among patients, breast cancer remains the most common cancer among women and is the second leading cause of cancer death in women. The magnitude of this problem provides a strong impetus for new chemopreventative strategies and/or lifestyle changes that reduce cancer incidence. It is of significance, therefore, that several studies positively correlate obesity to the development of breast cancer. Importantly, obesity is also highly associated with elevated cholesterol, and cholesterol itself is a risk factor for breast cancer. Furthermore, patients taking statins demonstrate a lower breast cancer incidence and decreased recurrence. The recent observation that 27-hydroxycholesterol (27HC) is produced in a stoichiometric manner from cholesterol, together with our recent demonstration that it exerts partial agonist activity on both the estrogen and liver X receptors, suggested a potential mechanistic link between hyper-cholesterolemia and breast cancer incidence. Using genetic and pharmacological approaches, we have recently shown that elevation of circulating 27HC significantly increases tumor growth and metastasis in murine models of breast cancer. Further, we have demonstrated in appropriate animal models that the impact of high-fat diet on tumor pathogenesis can be mitigated by statins or by small molecule inhibitors of CYP27A1. These findings suggest that pharmacological or dietary modifications that lower total cholesterol, and by inference 27HC, are likely to reduce the impact of obesity/metabolic syndrome on breast cancer incidence.

Duke Scholars

Published In

Climacteric

DOI

EISSN

1473-0804

Publication Date

December 2014

Volume

17 Suppl 2

Issue

0 2

Start / End Page

60 / 65

Location

England

Related Subject Headings

  • Selective Estrogen Receptor Modulators
  • Risk Factors
  • Receptors, Estrogen
  • Paracrine Communication
  • Obstetrics & Reproductive Medicine
  • Obesity
  • Neoplasm Recurrence, Local
  • Incidence
  • Hyperlipidemias
  • Hydroxycholesterols
 

Citation

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Chicago
ICMJE
MLA
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McDonnell, D. P., Chang, C.-Y., & Nelson, E. R. (2014). The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer. Climacteric, 17 Suppl 2(0 2), 60–65. https://doi.org/10.3109/13697137.2014.966949
McDonnell, D. P., C. -. Y. Chang, and E. R. Nelson. “The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer.Climacteric 17 Suppl 2, no. 0 2 (December 2014): 60–65. https://doi.org/10.3109/13697137.2014.966949.
McDonnell DP, Chang C-Y, Nelson ER. The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer. Climacteric. 2014 Dec;17 Suppl 2(0 2):60–5.
McDonnell, D. P., et al. “The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer.Climacteric, vol. 17 Suppl 2, no. 0 2, Dec. 2014, pp. 60–65. Pubmed, doi:10.3109/13697137.2014.966949.
McDonnell DP, Chang C-Y, Nelson ER. The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer. Climacteric. 2014 Dec;17 Suppl 2(0 2):60–65.

Published In

Climacteric

DOI

EISSN

1473-0804

Publication Date

December 2014

Volume

17 Suppl 2

Issue

0 2

Start / End Page

60 / 65

Location

England

Related Subject Headings

  • Selective Estrogen Receptor Modulators
  • Risk Factors
  • Receptors, Estrogen
  • Paracrine Communication
  • Obstetrics & Reproductive Medicine
  • Obesity
  • Neoplasm Recurrence, Local
  • Incidence
  • Hyperlipidemias
  • Hydroxycholesterols