Cancer Center, L913, Department of Medicine, Boston University School of Medicine, 72 E Concord St, Boston, MA 02118, U.S.A.
Anticancer Res. 2014 Mar;34(3):1071-7.
Although breast cancer is a heterogeneous disease that is challenging to characterize and treat, the recent explosion of genetic and epigenetic research may help improve these endeavors. In the present review, we use genetic diversity to characterize and classify different types of breast cancer. We also discuss genetic and epigenetic changes that are involved in the development of different breast cancer types and examine how these changes affect prognosis. It appears that while a combination of mutations and copy number changes determine the type of breast cancer, epigenetic alterations may be the primary initiators of cancer development. Understanding these critical biomarkers and molecular changes will advance our ability to effectively treat breast cancer. Next, we examine potential drug therapies directed at epigenetic changes, as such epigenetic drug treatments may prove useful for treating patient-specific tumors, breast cancer progenitor cells, and drug-resistant cells. Lastly, we discuss on mechanisms of carcinogenesis, including a novel hypothesis outlining the role of epigenetics in the development of cancer progenitor cells and metastasis. Overall, breast cancer subtypes may have a similar epigenetic signal that promotes cancer development, and treatment may be most effective if both epigenetic and genetic differences are targeted.
虽然乳腺癌是一种具有异质性的疾病，难以进行特征描述和治疗，但最近遗传和表观遗传学研究的爆炸式发展可能有助于改善这些努力。在本综述中，我们使用遗传多样性来描述和分类不同类型的乳腺癌。我们还讨论了涉及不同类型乳腺癌发展的遗传和表观遗传变化，并研究了这些变化如何影响预后。似乎虽然突变和拷贝数变化的组合决定了乳腺癌的类型，但表观遗传改变可能是癌症发展的主要启动因素。了解这些关键的生物标志物和分子变化将提高我们有效治疗乳腺癌的能力。接下来，我们研究了针对表观遗传变化的潜在药物治疗方法，因为这种表观遗传药物治疗可能对治疗特定于患者的肿瘤、乳腺癌祖细胞和耐药细胞有用。最后，我们讨论了致癌机制，包括一个新的假说，该假说概述了表观遗传学在癌症祖细胞和转移发展中的作用。总体而言，乳腺癌亚型可能具有相似的促进癌症发展的表观遗传信号，如果同时针对表观遗传和遗传差异进行治疗，效果可能最佳。
