A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk

作者：Vinayak Shaveta; Schwartz Erich J; Jensen Kristin; Lipson Jafi; Alli Elizabeth; McPherson Lisa; Fernandez Adrian M; Sharma Vandana B; Staton Ashley; Mills Meredith A; Schackmann Elizabeth A; Telli Melinda L; Kardashian Ani; Ford James M; Kurian Allison W^*

来源：Breast Cancer Research and Treatment, 2013, 142(2): 389-398.

DOI：10.1007/s10549-013-2739-z

• Breast cancer
• Cancer prevention
• Cancer risk reduction
• BRCA1/2
• Lovastatin
• Clinical trial
• Biomarkers
• Random periareolar fine needle aspiration

Pre-clinical and epidemiologic studies provide rationale for evaluating lipophilic statins for breast cancer prevention. We conducted a single-arm, biomarker modulation trial of lovastatin among women with increased risk of breast cancer. Eligibility criteria included a deleterious germline mutation in BRCA1, BRCA2, CDH1, or TP53; lifetime breast cancer risk of a parts per thousand yen20 % as estimated by the Claus model; or personal history of estrogen receptor and progesterone receptor-negative breast cancer. Participants received 40 mg of lovastatin orally twice daily for 6 months. We evaluated the following biomarkers before and after lovastatin use: breast duct cytology (primary endpoint), serum lipids, C-reactive protein, insulin-like growth factor-1, IGF binding protein-3, lipid peroxidation, oxidative DNA damage, 3-hydroxy-3-methylglutaryl CoA reductase genotype, and mammographic density. Thirty women were enrolled, and 26 (86.7 %) completed the study. For the primary endpoint of changes in breast duct cytology sampled by random periareolar fine needle aspiration, most participants [57.7 %, 95 % confidence interval (CI) 38.9-74.5 %] showed no change after lovastatin; 19.2 % (CI 8.1-38.3 %) had a favorable change in cytology, 7.7 % (95 % CI 1.0-25.3 %) had an unfavorable change, and 15.4 % (95 % CI 5.5-34.2 %) had equivocal results due to acellular specimens, usually after lovastatin. No significant changes were observed in secondary biomarker endpoints. The study was generally well-tolerated: 4 (13.3 %) participants did not complete the study, and one (3.8 %) required a dose reduction. This trial was technically feasible, but demonstrated no significant biomarker modulation; contributing factors may include insufficient sample size, drug dose and/or duration. The results are inconclusive and do not exclude a favorable effect on breast cancer risk.

• 出版日期2013-11