The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRBI, Room 144, Baltimore, MD 21231, USA.
Breast Cancer Res Treat. 2012 Feb;131(3):915-24. doi: 10.1007/s10549-011-1858-7. Epub 2011 Nov 11.
Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0-III breast cancer received simvastatin 40 mg orally daily for 24-28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation.
观察性研究表明，使用 HMG-CoA 还原酶抑制剂（他汀类药物）的患者癌症发病率降低，且被诊断患有早期乳腺癌的他汀类药物使用者的复发风险降低。我们启动了一项前瞻性研究，以确定可以在未来试验中验证的辛伐他汀化学预防活性的潜在生物标志物。先前患有乳腺癌的女性的对侧乳房被用作高危模型。符合条件的女性已完成先前 0-III 期乳腺癌的所有计划治疗，每天口服辛伐他汀 40mg 持续 24-28 周。在基线和研究结束时，我们测量了循环中的高敏 C 反应蛋白（hsCRP）、雌激素和空腹血脂；对侧乳房乳腺 X 线照片上的乳房密度；以及 Rand 简短形式 36 项健康调查的生活质量。共纳入 50 名女性，中位年龄为 53 岁。总胆固醇、LDL 胆固醇、甘油三酯和 hsCRP 在研究期间显著下降（P 值均<0.001、<0.001、0.003 和 0.05）。雌酮硫酸酯浓度随辛伐他汀治疗而降低（总体 P=0.01），尤其是在绝经后参与者中（P=0.006）。我们未观察到循环雌二醇或雌酮浓度、对侧乳房 X 线照片上的乳房密度或报告的身体机能或疼痛评分有显著变化。这项研究证明了使用高危女性对侧乳房进行短期生物标志物调节研究的可行性。辛伐他汀似乎调节了雌酮硫酸酯浓度及其在乳腺癌中的潜在化学预防活性，值得进一步研究。
