Breast Cancer Signaling and Therapeutics Team, Program in Molecular Oncology and Pre-clinical Therapeutics, Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI, USA.
Laboratory of microRNA Diagnostics and Therapeutics, Program in Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI, USA.
Breast Cancer (Dove Med Press). 2015 Feb 23;7:59-79. doi: 10.2147/BCTT.S43799. eCollection 2015.
Breast cancer is a complex and heterogeneous disease. Signaling by estrogen receptor (ER), progesterone receptor (PR), and/or human EGF-like receptor 2 (HER2) is a main driver in the development and progression of a large majority of breast tumors. Molecular characterization of primary tumors has identified major subtypes that correlate with ER/PR/HER2 status, and also subgroup divisions that indicate other molecular and cellular features of the tumors. While some of these research findings have been incorporated into clinical practice, several challenges remain to improve breast cancer management and patient survival, for which the integration of novel biomarkers into current practice should be beneficial. microRNAs (miRNAs) are a class of short non-coding regulatory RNAs with an etiological contribution to breast carcinogenesis. miRNA-based diagnostic and therapeutic applications are rapidly emerging as novel potential approaches to manage and treat breast cancer. Rapid technological development enables specific and sensitive detection of individual miRNAs or the entire miRNome in tissues, blood, and other biological specimens from breast cancer patients. This review focuses on recent miRNA research and its potential to address unmet clinical needs and challenges. The four sections presented discuss miRNA findings in the context of the following clinical challenges: biomarkers for early detection; prognostic and predictive biomarkers for treatment decisions using targeted therapies against ER and HER2; diagnostic and prognostic biomarkers for subgrouping of triple-negative breast cancer, for which there are currently no targeted therapies; and biomarkers for monitoring and characterization of metastatic breast cancer. The review concludes with a critical analysis of the current state of miRNA breast cancer research and the need for further studies using large patient cohorts under well-controlled conditions before considering the clinical implementation of miRNA biomarkers.
乳腺癌是一种复杂且异质性的疾病。雌激素受体（ER）、孕激素受体（PR）和/或人类表皮生长因子受体 2（HER2）的信号传导是绝大多数乳腺癌发展和进展的主要驱动因素。对原发性肿瘤的分子特征分析确定了与 ER/PR/HER2 状态相关的主要亚型，以及指示肿瘤其他分子和细胞特征的亚组划分。虽然其中一些研究发现已纳入临床实践，但仍存在一些挑战，需要改善乳腺癌的管理和患者的生存，为此，将新的生物标志物纳入当前实践应该是有益的。 microRNAs (miRNAs) 是一类短的非编码调控 RNA，对乳腺癌的发生有病因学贡献。基于 miRNA 的诊断和治疗应用作为管理和治疗乳腺癌的新的潜在方法正在迅速出现。快速的技术发展使能够在组织、血液和来自乳腺癌患者的其他生物标本中特异性和敏感地检测单个 miRNA 或整个 miRNome。这篇综述重点介绍了最近的 miRNA 研究及其解决未满足的临床需求和挑战的潜力。所呈现的四个部分讨论了 miRNA 研究结果及其在以下临床挑战中的潜在应用：早期检测的生物标志物；针对 ER 和 HER2 的靶向治疗决策的预后和预测生物标志物；三阴性乳腺癌亚组的诊断和预后生物标志物，目前尚无针对该亚组的靶向治疗；以及用于监测和表征转移性乳腺癌的生物标志物。综述最后对 miRNA 乳腺癌研究的现状进行了批判性分析，并需要在考虑 miRNA 生物标志物的临床实施之前，使用大的患者队列在良好控制的条件下进行进一步研究。
