title: A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer.
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.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRBI, Room 144, Baltimore, MD 21231, USA.
authors.forename: Michaela J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Prowell
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Blackford
authors.forename: Celia
authors.initials: C
authors.lastname: Byrne
authors.forename: Nagi F
authors.initials: NF
authors.lastname: Khouri
authors.forename: Shannon A
authors.initials: SA
authors.lastname: Slater
authors.forename: Stacie C
authors.initials: SC
authors.lastname: Jeter
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Leisha A
authors.initials: LA
authors.lastname: Emens
authors.forename: John H
authors.initials: JH
authors.lastname: Fetting
authors.forename: Pendleton P
authors.initials: PP
authors.lastname: Powers
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Hannah
authors.initials: H
authors.lastname: Green
authors.forename: Jacklyn N
authors.initials: JN
authors.lastname: Thibert
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Folkerd
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D011788:Quality of Life; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D002097:C-Reactive Protein; D019821:Simvastatin; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
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