Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer Journal Article
| Authors: | Garwood, E. R.; Kumar, A. S.; Baehner, F. L.; Moore, D. H.; Au, A.; Hylton, N.; Flowers, C. I.; Garber, J.; Lesnikoski, B. A.; Hwang, E. S.; Olopade, O.; Port, E. R.; Campbell, M.; Esserman, L. J. |
| Article Title: | Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer |
| 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. © 2009 Springer Science+Business Media, LLC. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; middle aged; cancer surgery; clinical trial; treatment duration; comparative study; cancer staging; nuclear magnetic resonance imaging; cancer grading; ki 67 antigen; cell proliferation; ki-67 antigen; biological marker; c reactive protein; protein blood level; cancer prevention; chemoprophylaxis; low drug dose; apoptosis; controlled clinical trial; breast cancer; tumor volume; randomized controlled trial; c-reactive protein; caspase 3; drug effect; breast neoplasms; gene expression regulation, neoplastic; carcinoma in situ; cholesterol; cholesterol blood level; perioperative period; estrogen receptor; indoles; intraductal carcinoma; carcinoma, intraductal, noninfiltrating; protein cleavage; breast biopsy; blood examination; fluindostatin; hydroxymethylglutaryl-coa reductase inhibitors; dcis ductal carcinoma in situ; hmg-coa reductase inhibitors; statin(s); fatty acids, monounsaturated |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 119 |
| Issue: | 1 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2010-01-01 |
| Start Page: | 137 |
| End Page: | 144 |
| Language: | English |
| DOI: | 10.1007/s10549-009-0507-x |
| PUBMED: | 19728082 |
| PROVIDER: | scopus |
| PMCID: | PMC4087110 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "CODEN: BCTRD" - "Source: Scopus" |
