Radiation Oncology Department and Henri Mondor Breast Center, AP-HP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, 94010, Créteil, France.
INSERM Unit 955, Immunoregulation and Biotherapy (I-Biot) Team, Mondor Institute of Biomedical Research (IMRB), Créteil, France.
Breast Cancer Res Treat. 2022 Jun;193(2):265-279. doi: 10.1007/s10549-022-06533-3. Epub 2022 Apr 9.
Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values.
A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis.
Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT.
miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients' settings.
三阴性乳腺癌（TNBC）的放射治疗（RT）目前用于辅助治疗，并正在作为新辅助治疗的辅助手段进行研究。然而，TNBC 的放射抵抗仍然是一个障碍，因此需要新的生物标志物来选择接受 RT 治疗的患者，以整合到 TNBC 治疗方案中。微小 RNA（miRs）是基因表达的重要调控因子，参与癌症对电离辐射（IR）的反应，并可通过肿瘤组织或液体活检进行评估。本系统评价旨在评估 miRs 与 TNBC 对辐射的反应之间的关系，以及它们在预测和预后方面的潜在价值。
在 PubMed、EMBASE 和 Web of Science 上全面检索与 TNBC 中 miRs 和 RT 相关的研究。我们搜索了涉及 TNBC 相关临床前和临床研究中 miRs 对 IR 反应失调的原始英文文章。经过严格筛选，选择了 44 项研究进行进一步分析。
确定了 35 种与 TNBC 相关的 miRs，其中 21 种下调，13 种上调，2 种在这种癌症中具有双面表达。其中许多 miRs 的表达调节具有放射增敏作用，其中 miR-7、-27a、-34a、-122 和 let-7 研究最多，但仍仅在实验模型中进行。报道对 IR 反应影响/反映最大的 miRs 是 miR-7、-27a、-155、-205、-211 和 -221，而 miR-21、-33a、-139-5p 和 -210 与接受 RT 治疗后的 TNBC 患者预后相关。
miRs 是 TNBC 中的新兴生物标志物和放射增敏剂，值得进一步研究。循环 miRs 的动态评估可以改善监测和 TNBC RT 疗效，这在新辅助治疗和高危患者的环境中特别有意义。
