German Cancer Research Center, Division of Cancer Epidemiology, Heidelberg, Germany.
University Medical Center Hamburg-Eppendorf, Department of Cancer Epidemiology/ Clinical Cancer Registry, University Cancer Center Hamburg, Hamburg, Germany.
Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700449. Epub 2017 Sep 1.
Phytoestrogens (PE) may improve breast cancer prognosis by modifying tumor prognostic markers, such as cell proliferation marker Ki-67 and human epidermal growth factor receptor 2 (HER2). Epidemiological evidence linking lignans and isoflavones to Ki-67 and HER2 is limited. We examined associations between the major metabolites of lignans and isoflavones - enterolactone (ENL) and genistein (GEN) - respectively, and Ki-67 expression and HER2 in tumor tissue of breast cancer patients.
Data from 1060 invasive breast cancer patients from the population-based MARIE study were used. Multivariate-adjusted linear (Ki-67 log-transformed) and quantile regression, and logistic regression analyses (HER2, Ki-67 dichotomized) were performed to calculate β estimates and ORs, respectively. Median post-diagnostic ENL and GEN concentrations were 19.5 and 4.8 nmol/L, respectively. Median Ki-67 was 12.0%, and 21.2% of the tumors were HER2+. After adjustment, there was an inverse association between GEN and Ki-67 at high expression levels (OR for Ki-67 ≥20% versus <20% of 0.93 (95%CI [0.87;0.99]) per 10 nmol/L GEN increment).
Our findings indicate an inverse association between GEN and Ki-67 at high levels of Ki-67 expression. Additional investigations are recommended to confirm our findings and to further elucidate mechanisms linking PE metabolites to breast cancer survival.
植物雌激素 (PE) 可以通过改变肿瘤预后标志物来改善乳腺癌的预后，例如细胞增殖标志物 Ki-67 和人表皮生长因子受体 2 (HER2)。将木脂素和异黄酮与 Ki-67 和 HER2 联系起来的流行病学证据有限。我们研究了木脂素和异黄酮的主要代谢物 - 肠内酯 (ENL) 和染料木黄酮 (GEN) - 分别与乳腺癌患者肿瘤组织中的 Ki-67 表达和 HER2 之间的关联。
使用基于人群的 MARIE 研究中 1060 名浸润性乳腺癌患者的数据。进行了多变量调整的线性（Ki-67 对数转换）和分位数回归以及逻辑回归分析（HER2，Ki-67 二分），以分别计算β估计值和 OR。诊断后 ENL 和 GEN 的中位数浓度分别为 19.5 和 4.8 nmol/L。中位数 Ki-67 为 12.0%，21.2%的肿瘤为 HER2+。调整后，GEN 与 Ki-67 在高表达水平之间呈负相关（Ki-67≥20%与<20%的比值比为 0.93 [95%CI [0.87;0.99]）。
我们的研究结果表明，在 Ki-67 高表达水平时，GEN 与 Ki-67 之间呈负相关。建议进行进一步的研究以证实我们的发现，并进一步阐明 PE 代谢物与乳腺癌生存之间的联系机制。
