Fluvastatin reduces proliferation and increases apoptosis  in women with high grade breast cancer.
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.
Garwood
Elisabeth R
ER
Department of Surgery, University of California, San Francisco, CA, USA.
Kumar
Anjali S
AS
Baehner
Frederick L
FL
Moore
Dan H
DH
Au
Alfred
A
Hylton
Nola
N
Flowers
Chris I
CI
Garber
Judy
J
Lesnikoski
Beth-Ann
BA
Hwang
E Shelley
ES
Olopade
Olofunmilao
O
Port
Elisa Rush
ER
Campbell
Michael
M
Esserman
Laura J
LJ
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000096:biosynthesis; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy*; D053148:Caspase 3 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D019394:Ki-67 Antigen; D000077340:Fluvastatin; D002097:C-Reactive Protein; D053148:Caspase 3