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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-02

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

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. More... »

PAGES

915-924

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-011-1858-7

DOI

http://dx.doi.org/10.1007/s10549-011-1858-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030262933

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22076478


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