International Journal of Cancer, 2015, 137(12):2785–2794.

The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment

Clemence Basse, Michel Arock

Medical Oncology Unit, Anticancer Center Henri Becquerel, Rouen, France; Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France

Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore, epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then expose the future role that control of epigenetic modifications might play in prevention, prognostication, follow-up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi-drugs might have an increasing potential of development in the next future. However, if DNA methyltransferase inhibitors and histone desacetylase inhibitors have shown encouraging results in BC, their action remains nonspecific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in cotreatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi-drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of isothiocyanates from cruciferous vegetables or of Genistein from soybean in a dietary program that might potentially reduce the risk of BC in large populations.

美国《国际癌症杂志》，2015年12月

表观遗传学在乳腺癌中日益重要的作用︰ 对致病性、 生物标志物、 预防和治疗的影响

克莱门斯 巴斯，米歇尔 阿柔克

法国亨利贝克勒尔抗癌中心肿瘤医学部；法国巴黎高等师范学校分子肿瘤学和药理学学院

现今，癌症发生的机制被认为是遗传缺陷和表观遗传修饰的后果。因此，表观遗传已成为一个非常有吸引力的研究领域，被越来越多地研究以找到预防和治疗肿瘤的新方法，特别是乳腺癌 (BC)。因此，本综述将首先研究癌症中已知的表观遗传修饰，然后揭示表观遗传修饰的控制今后在预防、 预测、 后续和 BC 的治疗中可能发挥的作用。事实上，在外周血中发现的表观遗传生物标志物可能成为检测BC的新工具，来定义其预后并预测其结果，而 epi 药物的潜力在未来可能有所增长。然而，如果 DNA 甲基转移酶抑制剂和组蛋白脱乙酰基酶抑制剂在BC治疗方面已经取得令人鼓舞的成果，它们的行动仍然是非特异性的。因此，需要更多的临床研究来确认这些分子更确切的疗效，即使在联合治疗期间它们提供例了令人鼓舞的结果。本综述还将确认RNA 干扰剂 (RNAi) 作为免疫药物的潜力。最后，我们将专注于通过基于饮食的表观遗传对BC的潜在预防，并且我们将重点研究十字花科蔬菜衍生的异硫氰酸盐或从豆科植物中获得的金雀异黄素，这些有可能降低很多人患BC的风险。