Phase I biomarker modulation study of atorvastatin in women at increased risk for breast cancer.
Selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene that reduce the risk of breast cancer are limited to only estrogen receptor-positive (ER(+)) breast cancer. In addition, patient acceptance of SERMs is low due to toxicity and intolerability. New agents with improved toxicity profile that reduce risk of ER-negative breast cancer are urgently needed. Observational studies show that statins can reduce breast cancer incidence and recurrence. The objective of this prospective short-term prevention study was to evaluate the effect of a lipophilic statin, atorvastatin, on biomarkers in breast tissue and serum of women at increased risk. Eligible participants included women with previous history of carcinoma in situ, or atypical hyperplasia, or 5 year breast cancer projected Gail risk >1.67 %, or lifetime breast cancer risk >20 % calculated by models including Claus, Tyrer-Cuzick, Boadicea, or BRCAPRO. Patients underwent baseline fine needle aspiration (FNA) of the breast, blood collection for biomarker analysis, and were randomized to either no treatment or atorvastatin at 10, 20, or 40 mg/day dose for 3 months. At 3 months, blood collection and breast FNA were repeated. Biomarkers included C-reactive protein (CRP), lipid profile, atorvastatin, and its metabolites, Ki-67, bcl-2, EGFR, and pEGFR. Baseline genotype for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) was also measured. Among 60 patients evaluated, a significant reduction in serum CRP, cholesterol and low-density lipoprotein (LDL), and increase in atorvastatin metabolites in serum and breast FNAs was demonstrated. No changes were observed in other tissue biomarkers. This study shows that atorvastatin and its metabolites are detectable in breast samples and may lower serum CRP among women without hyperlipidemia.
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA. barun@mdanderson.org.
Banu K
BK
Arun
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Yun
Y
Gong
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Diane
D
Liu
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Jennifer K
JK
Litton
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Angelica M
AM
Gutierrez-Barrera
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J
J
Jack Lee
Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lana
L
Vornik
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Nuhad K
NK
Ibrahim
Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
Terri
T
Cornelison
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Gabriel N
GN
Hortobagyi
Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
Brandy M
BM
Heckman-Stoddard
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Kimberly B
KB
Koenig
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Ricardo R
RR
Alvarez
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
James L
JL
Murray
Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA.
Vicente
V
Valero
Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Scott M
SM
Lippman
Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Powel
P
Brown
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nour
N
Sneige
D000328:Adult; D000368:Aged; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D008077:Lipoproteins, LDL; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin
Atorvastatin; Breast cancer biomarkers; Breast cancer risk; Statins