Article

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

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRBI, Room 144, Baltimore, MD 21231, USA.
Breast Cancer Research and Treatment (impact factor: 4.43). 11/2011; 131(3):915-24. DOI:10.1007/s10549-011-1858-7 pp.915-24
Source: PubMed

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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Keywords

breast cancer warrants
 
contralateral breast
 
decreased incidence
 
Eligible women
 
estrone concentrations
 
Estrone sulfate concentrations
 
fasting lipids
 
future trials
 
high-risk women
 
high-sensitivity C-reactive protein
 
LDL cholesterol
 
median age
 
modulate estrone sulfate concentrations
 
potential biomarkers
 
potential chemopreventive activity
 
prospective study
 
significant change
 
simvastatin chemopreventive activity
 
statin users
 
Total cholesterol