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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2012

01-02-2012 | Clinical Trial

A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer

Authors: Michaela J. Higgins, Tatiana M. Prowell, Amanda L. Blackford, Celia Byrne, Nagi F. Khouri, Shannon A. Slater, Stacie C. Jeter, Deborah K. Armstrong, Nancy E. Davidson, Leisha A. Emens, John H. Fetting, Pendleton P. Powers, Antonio C. Wolff, Hannah Green, Jacklyn N. Thibert, James M. Rae, Elizabeth Folkerd, Mitchell Dowsett, Roger S. Blumenthal, Judy E. Garber, Vered Stearns

Published in: Breast Cancer Research and Treatment | Issue 3/2012

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Abstract

Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0–III breast cancer received simvastatin 40 mg orally daily for 24–28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation.
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Metadata
Title
A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer
Authors
Michaela J. Higgins
Tatiana M. Prowell
Amanda L. Blackford
Celia Byrne
Nagi F. Khouri
Shannon A. Slater
Stacie C. Jeter
Deborah K. Armstrong
Nancy E. Davidson
Leisha A. Emens
John H. Fetting
Pendleton P. Powers
Antonio C. Wolff
Hannah Green
Jacklyn N. Thibert
James M. Rae
Elizabeth Folkerd
Mitchell Dowsett
Roger S. Blumenthal
Judy E. Garber
Vered Stearns
Publication date
01-02-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-011-1858-7

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