Department of Gynecology and Obstetrics, Medical School, São Paulo State University (UNESP), Botucatu 18618-687, São Paulo, Brazil.
Hermínio Ometto Foundation, Araras 13607-339, São Paulo, Brazil.
Cells. 2020 May 8;9(5):1164. doi: 10.3390/cells9051164.
Evidence has emerged implicating epigenetic alterations in inflammatory breast cancer (IBC) origin and progression. IBC is a rare and rapidly progressing disease, considered the most aggressive type of breast cancer (BC). At clinical presentation, IBC is characterized by diffuse erythema, skin ridging, dermal lymphatic invasion, and peau d'orange aspect. The widespread distribution of the tumor as emboli throughout the breast and intra- and intertumor heterogeneity is associated with its poor prognosis. In this review, we highlighted studies documenting the essential roles of epigenetic mechanisms in remodeling chromatin and modulating gene expression during mammary gland differentiation and the development of IBC. Compiling evidence has emerged implicating epigenetic changes as a common denominator linking the main risk factors (socioeconomic status, environmental exposure to endocrine disruptors, racial disparities, and obesity) with IBC development. DNA methylation changes and their impact on the diagnosis, prognosis, and treatment of IBC are also described. Recent studies are focusing on the use of histone deacetylase inhibitors as promising epigenetic drugs for treating IBC. All efforts must be undertaken to unravel the epigenetic marks that drive this disease and how this knowledge could impact strategies to reduce the risk of IBC development and progression.
有证据表明表观遗传改变与炎症性乳腺癌（IBC）的起源和进展有关。IBC 是一种罕见且进展迅速的疾病，被认为是最具侵袭性的乳腺癌（BC）类型。在临床表现上，IBC 的特征是弥漫性红斑、皮肤起皱、真皮淋巴管浸润和橘皮样外观。肿瘤作为栓塞物广泛分布于乳房内以及肿瘤内和肿瘤间异质性与预后不良有关。在这篇综述中，我们强调了一些研究，这些研究记录了表观遗传机制在重塑染色质和调节乳腺分化和 IBC 发展过程中基因表达方面的重要作用。越来越多的证据表明，表观遗传变化是将主要风险因素（社会经济地位、环境暴露于内分泌干扰物、种族差异和肥胖）与 IBC 发展联系起来的共同因素。还描述了 DNA 甲基化变化及其对 IBC 的诊断、预后和治疗的影响。最近的研究集中在使用组蛋白去乙酰化酶抑制剂作为治疗 IBC 的有前途的表观遗传药物。必须尽一切努力揭示驱动这种疾病的表观遗传标记，以及这些知识如何影响降低 IBC 发展和进展风险的策略。
