Hydroxytyrosol, a component of olive oil for breast cancer prevention in women at high risk of cancer

This study evaluates the effects of hydroxytyrosol (HT), a component of olive oil, on mammographic breast density reduction. We explored effects of HT on Wnt ß-catenin and other pathways involved in cancer stem cell renewal, DNA repair, cell proliferation and differentiation. Hydroxytyrosol reduced breast density only in women over 60 years, especially in those with high baseline breast density. HT also reduced proliferation and affected Wnt signaling pathway. This study lays the foundation for future larger studies in exploring a natural compound with well tolerability and overall nontoxic profile for chemoprevention of breast cancer. Overall design: The trial was preregistered at http://clinicaltrials.gov/ (NCT02068092). 25mg/day oral dose of HT were given for 12 months in pre- and post-menopausal women at increased risk of breast cancer. Out of 51 patients enrolled, 41 completed the study. The annualized percent decrease in maximum mammographic volumetric breast density (Max VBD%) between baseline (BL) and end-of-treatment (EOT) was analyzed. RNA sequencing (RNA-Seq) and multiplex analysis was performed on the breast biopsies to compare the BL with EOT samples.

本研究评估了羟基酪醇（hydroxytyrosol, HT）——橄榄油的一种活性成分——对乳腺钼靶密度降低的影响。我们探究了HT对Wnt β-连环蛋白及其他参与肿瘤干细胞更新、DNA修复、细胞增殖与分化的信号通路的调控作用。结果显示，羟基酪醇仅在60岁以上女性中可降低乳腺密度，尤其对基线乳腺密度较高的人群效果更为显著。此外，HT还可抑制细胞增殖并调控Wnt信号通路。本研究为后续开展更大规模的探索性研究奠定了基础，旨在筛选出耐受性良好、整体无毒的天然化合物用于乳腺癌化学预防。

试验设计：本试验已于http://clinicaltrials.gov/提前注册（登记号：NCT02068092）。针对乳腺癌风险升高的绝经前及绝经后女性，给予每日25mg的HT口服给药方案，持续12个月。入组的51例患者中，共41例完成了本研究。本研究分析了基线（BL）与治疗结束（EOT）时的最大乳腺钼靶体积密度（Max VBD%）的年化百分比降幅。通过对乳腺活检样本进行RNA测序（RNA-Seq）及多重分析，对比了基线与治疗结束时的样本差异。