Advancements in liquid biopsy for breast Cancer: Molecular biomarkers and clinical applications

Peng Qiu; Xiaopeng Yu; Fushuang Zheng; Xi Gu; QianQiu Huang; Ke Qin; Yueting Hu; Bowen Liu; Tianming Xu; Tao Zhang; Guanglei Chen; Yang Liu

doi:10.1016/j.ctrv.2025.102979

Advancements in liquid biopsy for breast Cancer: Molecular biomarkers and clinical applications

Cancer Treat Rev. 2025 Jun 14:139:102979. doi: 10.1016/j.ctrv.2025.102979. Online ahead of print.

Authors

Peng Qiu¹, Xiaopeng Yu², Fushuang Zheng³, Xi Gu², QianQiu Huang², Ke Qin², Yueting Hu², Bowen Liu², Tianming Xu², Tao Zhang⁴, Guanglei Chen⁵, Yang Liu⁶

Affiliations

¹ Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004 Liaoning Province, China.
² Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004 Liaoning Province, China.
³ Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004 Liaoning Province, China.
⁴ Department of Colorectal and Hernia Surgery, The Fourth Affiliated Hospital of China Medical University, 110004 Shenyang, Liaoning, China.
⁵ Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004 Liaoning Province, China. Electronic address: glchen@cmu.edu.cn.
⁶ Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004 Liaoning Province, China. Electronic address: 13998843583@163.com.

PMID: 40540857
DOI: 10.1016/j.ctrv.2025.102979

Abstract

Breast cancer is characterized by significant molecular heterogeneity; therefore, there are distinct clinical features, treatment modalities, and prognostic outcomes across its various molecular subtypes. In the era of precision medicine, liquid biopsy has emerged as a convenient and minimally invasive technique capable of dynamically representing the comprehensive tumor gene spectrum. This review systematically elaborates the clinical value of liquid biopsy as a breakthrough tool for precision diagnosis and treatment in breast cancer through dynamic detection of key biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and non-coding RNA (ncRNA). Specific genetic mutations and methylation signatures in ctDNA can be applied to early breast cancer screening, minimal residual disease monitoring, and tracking drug resistance mechanisms. CTCs enumeration (≥1/7.5 mL in early-stage cancer or ≥ 5/7.5 mL in metastatic cancer) and PD-L1 expression levels demonstrate direct correlations with prognostic stratification and the efficacy of immunotherapy. As the specificity and sensitivity of liquid biopsy continue to improve, personalized treatment strategies, informed by biomarker analysis and targeted precision therapies, have unveiled new avenues of hope for patients with breast cancer. However, several challenges persist in the practical application of liquid biopsy. Despite persistent challenges, such as insufficient standardization and difficulties in resolving low-abundance variants, future advancements should focus on multi-omics integration and AI-driven technological breakthroughs to overcome bottlenecks in clinical translation. This review summarizes cutting-edge liquid biopsy technologies for identifying clinically significant molecular biomarkers, focusing on discussing critical challenges in the strategies to advance precision oncology applications for optimized treatment guidance and disease surveillance in breast cancer.

Keywords: Breast cancer; Circulating tumor DNA; Circulating tumor cells; Exosome; Liquid biopsy; ncRNA.

Publication types

Review