We conducted a multiinstitutional, placebo-controlled phase IIB trial of the lignan secoisolariciresinol diglucoside (SDG) found in flaxseed. Benign breast tissue was acquired by random periareolar fine needle aspiration (RPFNA) from premenopausal women at increased risk for breast cancer. Those with hyperplasia and ≥2% Ki-67 positive cells were eligible for randomization 2:1 to 50 mg SDG/day (Brevail) versus placebo for 12 months with repeat bio-specimen acquisition. The primary endpoint was difference in change in Ki-67 between randomization groups. A total of 180 women were randomized, with 152 ultimately evaluable for the primary endpoint. Median baseline Ki-67 was 4.1% with no difference between arms. Median Ki-67 change was −1.8% in the SDG arm (P = 0.001) and −1.2% for placebo (P = 0.034); with no significant difference between arms. As menstrual cycle phase affects proliferation, secondary analysis was performed for 117 women who by progesterone levels were in the same phase of the menstrual cycle at baseline and off-study tissue sampling. The significant Ki-67 decrease persisted for SDG (median = −2.2%; P = 0.002) but not placebo (median = −1.0%). qRT-PCR was performed on 77 pairs of tissue specimens. Twenty-two had significant ERα gene expression changes (<0.5 or >2.0) with 7 of 10 increases in placebo and 10 of 12 decreases for SDG (P = 0.028), and a difference between arms (P = 0.017). Adverse event incidence was similar in both groups, with no evidence that 50 mg/day SDG is harmful. Although the proliferation biomarker analysis showed no difference between the treatment group and the placebo, the trial demonstrated use of SDG is tolerable and safe.

中文翻译：

---

木脂素开环异落叶松树脂醇二葡萄糖苷对乳腺癌风险增加的绝经前妇女的随机 IIB 期试验


我们对亚麻籽中发现的木酚素开环异落叶松树脂醇二葡萄糖苷 (SDG) 进行了一项多机构、安慰剂对照的 IIB 期试验。良性乳腺组织是通过随机乳晕周围细针抽吸术（RPFNA）从乳腺癌风险较高的绝经前女性身上获取的。那些增生且 Ki-67 阳性细胞≥2% 的患者有资格接受随机分组，剂量为 2:1 至 50 mg SDG/天 (Brevail)，与安慰剂相比，持续 12 个月，并重复采集生物样本。主要终点是随机分组之间 Ki-67 变化的差异。共有 180 名女性被随机分组​​，其中 152 名女性最终可进行主要终点评估。中位基线 Ki-67 为 4.1%，各组之间没有差异。 SDG 组的 Ki-67 变化中位数为 -1.8%（P = 0.001），安慰剂组为 -1.2%（P = 0.034）；臂间无显着差异。由于月经周期阶段影响增殖，因此对 117 名女性进行了二次分析，这些女性的孕酮水平在基线和研究外组织取样时处于月经周期的同一阶段。 SDG 组 Ki-67 持续显着下降（中位数 = -2.2%；P = 0.002），但安慰剂组则不然（中位数 = -1.0%）。对 77 对组织样本进行 qRT-PCR。 22 例患者的 ERα 基因表达发生显着变化 (<0 id=9>2.0)，安慰剂组 10 例中 7 例升高，SDG 组 12 例中 10 例降低 (P = 0.028)，两组之间存在差异 (P = 0.017)。两组的不良事件发生率相似，没有证据表明 50 毫克/天的 SDG 有害。尽管增殖生物标志物分析显示治疗组和安慰剂之间没有差异，但试验证明 SDG 的使用是可耐受且安全的。