A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer
- Describe changes from baseline in a panel of biomarkers (high-sensitivity C-reactive
protein [hsCRP], lipid profile, circulating estrogens, and contralateral breast
density) in women at high risk of developing new breast cancer who have undergone
surgical resection for history of ductal carcinoma in situ or stage I-III invasive
breast cancer treated with simvastatin.
- Correlate changes in the panel of biomarkers with wild-type versus polymorphic
3-hydroxyl-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in women treated with
- Evaluate methylation status across a panel of genes that are known to be frequently and
specifically hypermethylated in ductal carcinoma in situ (DCIS) and invasive breast
cancer (estrogen receptor [ER]-α and ER-β, cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1)
and correlate change in cumulative methylation with change in hsCRP, lipid profile,
contralateral breast density, estrogen concentrations, and pharmacogenetics.
- Measure changes in the phosphoinositide 3'-kinase (PI3K)/protein kinase B (Akt)
signaling pathway (Akt and p-Akt) before and after treatment with simvastatin.
OUTLINE: This is a multicenter study. Patients are stratified according to menopausal status
(pre- vs post-menopausal).
Patients receive oral simvastatin once daily for 24-28 weeks in the absence of disease
progression or unacceptable toxicity.
Patients undergo blood collection at baseline and at the end of study treatment for
pharmacogenetic and biomarker correlative studies. Patients undergo mammography and
measurement of breast density of the contralateral breast at baseline and at the end of
Quality of life is assessed at baseline and at the end of study treatment.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline
Baseline and week 24
Vered Stearns, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|