ABSTRACT

The stage and molecular pathology-dependent prognosis of breast cancer, the limited treatment options for triple-negative carcinomas, as well as the development of resistance to therapies illustrate the need for improved early diagnosis and the development of new therapeutic approaches. Increasing data suggests that some answers to these challenges could be found in the area of epigenetics. In this study, we focus on the current research of the epigenetics of breast cancer, especially on the potential of epigenetics for clinical application in diagnostics, risk stratification and therapy. The differential DNA methylation status of specific gene regions has been used in the past to differentiate breast cancer cells from normal tissue. New technologies as detection of circulating nucleic acids including microRNAs to early detect breast cancer are emerging. Pattern of DNA methylation and expression of histone-modifying enzymes have been successfully used for risk stratification. However, all these epigenetic biomarkers should be validated in larger clinical studies. Recent preclinical and clinical studies show a therapeutic benefit of epigenetically active drugs for breast cancer entities that are still difficult to treat (triple negative, UICC stage IV). Remarkably, epigenetic therapies combined with chemotherapies or hormone-based therapies represent the most promising strategy. At the current stage, the integration of epigenetic substances into established breast cancer therapy protocols seems to hold the greatest potential for a clinical application of epigenetic research.

摘要

乳腺癌的分期和分子病理学依赖性预后、三阴性癌的有限治疗选择以及对治疗的耐药性的发展表明需要改进早期诊断和开发新的治疗方法。越来越多的数据表明，这些挑战的一些答案可以在表观遗传学领域找到。在这项研究中，我们重点关注当前对乳腺癌表观遗传学的研究，特别是表观遗传学在诊断、风险分层和治疗方面的临床应用潜力。过去，特定基因区域的差异 DNA 甲基化状态已被用于区分乳腺癌细胞和正常组织。检测循环核酸（包括 microRNA）以早期检测乳腺癌的新技术正在出现。DNA 甲基化模式和组蛋白修饰酶的表达已成功用于风险分层。然而，所有这些表观遗传生物标志物都应该在更大规模的临床研究中得到验证。最近的临床前和临床研究表明，表观遗传活性药物对仍然难以治疗的乳腺癌实体（三阴性，UICC IV 期）具有治疗益处。值得注意的是，表观遗传疗法与化学疗法或基于激素的疗法相结合是最有希望的策略。在现阶段，将表观遗传物质整合到已建立的乳腺癌治疗方案中似乎具有表观遗传研究临床应用的最大潜力。