Reduction in Ki-67 in Benign Breast Tissue of High-Risk Women with the Lignan Secoisolariciresinol Diglycoside
Reduction in Ki-67 in Benign Breast Tissue of High-Risk Women with the Lignan Secoisolariciresinol Diglycoside
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DOI：
10.1158/1940-6207.capr-10-0022
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发表时间：
2010-10-01
影响因子：
3.3
通讯作者：
Johnson, Karen A.
中科院分区：
文献类型：
--
作者：
Fabian, Carol J.;Kimler, Bruce F.;Johnson, Karen A.
临床前和相关研究表明，减少乳腺癌与较高的木脂素摄入量或血液水平。我们进行了一项初步研究，在给予植物木脂素开环异落叶松树脂酚作为双糖苷（SDG）后，绝经前妇女乳腺癌风险生物标志物的调节。入选标准包括月经周期规律、未使用口服避孕药、5年风险增加>3倍、月经周期卵泡期随机乳晕周围细针穿刺（RPFNA）乳腺组织增生区基线Ki-67 ≥ 2%。SDG（50 mg/d）治疗12个月后重复RPFNA治疗。主要终点是Ki-67的变化。次要终点包括细胞形态学、乳腺摄影乳腺密度、血清生物可利用雌二醇和睾酮、胰岛素样生长因子-I和IGF结合蛋白-3以及血浆木脂素水平的变化。49名符合条件的女性中有45名完成了研究，具有良好的依从性（中位数= 96%）和很少的严重副作用（4% 3级）。中位血浆肠内酯增加了9倍，总木脂素增加了16倍。45例可评价受试者中有36例（80%）显示Ki-67降低，中位数从4%（范围，2-16.8%）降至2%（范围，0-15.2%; P < 0.001，Wilcoxon符号秩检验）。还观察到非典型细胞学检查女性比例较基线降低（P = 0.035）。基于有利的风险生物标志物调节和缺乏不良事件，我们正在绝经前妇女中开展SDG与安慰剂的随机试验。Cancer Prev Res; 3（10）; 1342-50. (c)2010年AACR。
Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a >3-fold increase in 5-year risk, and baseline Ki-67 of >= 2% in areas of hyperplasia in breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG (50 mg/d) was given for 12 months, followed by repeat RPFNA. The primary end point was change in Ki-67. Secondary end points included change in cytomorphology, mammographic breast density, serum bioavailable estradiol and testosterone insulin-like growth factor-I and IGF-binding protein-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased similar to 9-fold, and total lignans increased 16-fold. Thirty-six (80%) of the 45 evaluable subjects showed a decrease in Ki-67, from a median of 4% (range, 2-16.8%) to 2% (range, 0-15.2%; P < 0.001, Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (P = 0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG versus placebo in premenopausal women. Cancer Prev Res; 3(10); 1342-50. (c) 2010 AACR.