NDLI: Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer

Content Provider	PubMed Central
Author	Garwood, Elisabeth R. Kumar, Anjali S. Baehner, Frederick L. Moore, Dan H. Au, Alfred Hylton, Nola Flowers, Chris I. Garber, Judy Lesnikoski, Beth-ann Hwang, E. Shelley Olopade, Olofunmilao Port, Elisa Rush Campbell, Michael Esserman, Laura J.
Copyright Year	2009
Abstract	The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3–6 weeks before surgery. Tissue (diagnostic core biopsy/final surgical specimen), blood, and magnetic resonance images were obtained before/after treatment. The primary endpoint was Ki-67 (proliferation) reduction. Secondary endpoints were change in cleaved caspase-3 (CC3, apoptosis), MRI tumor volume, and serum C-reactive protein (CRP, inflammation). Planned subgroup analyses compared disease grade, statin dose, and estrogen-receptor status. Forty of 45 patients who enrolled completed the protocol; 29 had paired Ki-67 primary endpoint data. Proliferation of high grade tumors decreased by a median of 7.2% (P = 0.008), which was statistically greater than the 0.3% decrease for low grade tumors. Paired data for CC3 showed tumor apoptosis increased in 38%, remained stable in 41%, and decreased in 21% of subjects. More high grade tumors had an increase in apoptosis (60 vs. 13%; P = 0.015). Serum CRP did not change, but cholesterol levels were significantly lower post statin exposure (P<0.001). Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer. Effects were only evident in high grade tumors. These results support further evaluation of statins as chemoprevention for ER-negative high grade breast cancers.
Related Links	http://dx.doi.org/10.1007/s10549-009-0507-x
Ending Page	144
Page Count	8
Starting Page	137
File Format	PDF
ISSN	01676806
e-ISSN	15737217
Journal	Breast cancer research and treatment
Issue Number	1
Volume Number	119
Language	English
Publisher Date	2010-01-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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