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

Elisabeth R. Garwood, Anjali S. Kumar, Frederick L. Baehner, Dan H. Moore, Alfred Au, Nola Hylton, Chris I. Flowers, Judy Garber, Beth Ann Lesnikoski, E. Shelley Hwang, Olofunmilao Olopade, Elisa Rush Port, Michael Campbell, Laura J. Esserman

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalBreast Cancer Research and Treatment
Volume119
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • Breast cancer
  • Cancer prevention
  • DCIS ductal carcinoma in situ
  • HMG-CoA reductase inhibitors
  • Statin(s)

Fingerprint

Dive into the research topics of 'Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer'. Together they form a unique fingerprint.

Cite this