Puri Akshjot, Yin Zheng, Granados-Principal Sergio, Ensor Joe, Guzman Liliana, Rosato Roberto, Zhao Hong, Wong Stephen, Wang Lin, Patel Tejal, Chang Jenny C
Department of Hematology and Oncology, Houston Methodist Dr Mary and Ron Neal Cancer Center, Houston, Texas, USA.
Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston, Texas, USA.
Int J Breast Cancer. 2025 Jan 21;2025:8831168. doi: 10.1155/ijbc/8831168. eCollection 2025.
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 -catenin and other pathways involved in cancer stem cell renewal, DNA repair, cell proliferation, and differentiation. Twenty-five milligrams per day oral dose of HT was given for 12 months in pre- and postmenopausal 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. Max VBD% showed a nonsignificant change; however, in women 60 years or older, the max VBD% decrease was significant (3.7%, = 0.0391), especially in those with high BL mammographic density. Using RNA-Seq, 3330 unique transcripts were identified ( < 0.05). Mitotic telophase/cytokinesis and DNA damage were upregulated, whereas Wnt, Notch, and oxidative stress-induced senescence pathways were downregulated ( < 0.05). These pathways were confirmed by NanoString nCounter where significant decrease in proliferative genes (RELA and CDK4) and Wnt pathway (R-HSA-195721 and R-HAS-201681) was observed ( < 0.05). HT reduced breast density only in women over 60 years, especially in those with high BL breast density. HT also reduced proliferation and affected the 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. ClinicalTrials.gov identifier: NCT02068092.
本研究评估橄榄油成分羟基酪醇（HT）对乳腺钼靶密度降低的影响。我们探究了HT对Wnt -连环蛋白及其他参与癌症干细胞更新、DNA修复、细胞增殖和分化的信号通路的影响。对乳腺癌风险增加的绝经前和绝经后女性给予每日25毫克的口服HT剂量，为期12个月。在纳入的51例患者中，41例完成了研究。分析了基线（BL）和治疗结束（EOT）之间乳腺钼靶最大体积乳房密度（max VBD%）的年化百分比下降情况。对乳腺活检组织进行RNA测序（RNA-Seq）和多重分析，以比较BL和EOT样本。Max VBD%显示无显著变化；然而，在60岁及以上的女性中，max VBD%的下降是显著的（3.7%， = 0.0391），尤其是那些基线乳腺钼靶密度高的女性。使用RNA-Seq，鉴定出3330个独特转录本（ < 0.05）。有丝分裂末期/胞质分裂和DNA损伤上调，而Wnt、Notch和氧化应激诱导的衰老信号通路下调（ < 0.05）。这些信号通路通过NanoString nCounter得到证实，观察到增殖基因（RELA和CDK4）和Wnt信号通路（R-HSA-195721和R-HAS-201681）显著下降（ < 0.05）。HT仅在60岁以上的女性中降低了乳房密度，尤其是那些基线乳房密度高的女性。HT还降低了细胞增殖并影响了Wnt信号通路。本研究为未来更大规模的研究奠定了基础，以探索一种具有良好耐受性和总体无毒特性的天然化合物用于乳腺癌的化学预防。ClinicalTrials.gov标识符：NCT02068092。
