Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy.
Int J Mol Sci. 2023 Jan 16;24(2):1799. doi: 10.3390/ijms24021799.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer due to its molecular heterogeneity and poor clinical outcomes. Analysis of circulating cell-free tumor nucleic acids (ctNAs) can improve our understanding of TNBC and provide efficient and non-invasive clinical biomarkers that may be representative of tumor heterogeneity. In this review, we summarize the potential of ctNAs to aid TNBC diagnosis and prognosis. For example, tumor fraction of circulating cell-free DNA (TFx) may be useful for molecular prognosis of TNBC: high TFx levels after neoadjuvant chemotherapy have been associated with shorter progression-free survival and relapse-free survival. Mutations and copy number variations of TP53 and PIK3CA/AKT genes in plasma may be important markers of TNBC onset, progression, metastasis, and for clinical follow-up. In contrast, the expression profile of circulating cell-free tumor non-coding RNAs (ctncRNAs) can be predictive of molecular subtypes of breast cancer and thus aid in the identification of TBNC. Finally, dysregulation of some circulating cell-free tumor miRNAs (miR17, miR19a, miR19b, miR25, miR93, miR105, miR199a) may have a predictive value for chemotherapy resistance. In conclusion, a growing number of efforts are highlighting the potential of ctNAs for future clinical applications in the diagnosis, prognosis, and follow-up of TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，其具有分子异质性和较差的临床结局。循环游离肿瘤核酸（ctNAs）分析可以提高我们对 TNBC 的认识，并提供有效的、非侵入性的临床生物标志物，这些标志物可能代表肿瘤异质性。在这篇综述中，我们总结了 ctNAs 辅助 TNBC 诊断和预后的潜力。例如，循环游离 DNA 的肿瘤分数（TFx）可能对 TNBC 的分子预后有用：新辅助化疗后高 TFx 水平与无进展生存期和无复发生存期缩短相关。血浆中 TP53 和 PIK3CA/AKT 基因突变和拷贝数变异可能是 TNBC 发病、进展、转移的重要标志物，也可用于临床随访。相比之下，循环游离肿瘤非编码 RNA（ctncRNA）的表达谱可以预测乳腺癌的分子亚型，从而有助于识别 TNBC。最后，一些循环游离肿瘤 miRNA（miR17、miR19a、miR19b、miR25、miR93、miR105、miR199a）的失调可能对化疗耐药具有预测价值。总之，越来越多的研究强调了 ctNAs 在未来 TNBC 的诊断、预后和随访中的临床应用潜力。
