Binbin Cong,1,2 Xiaoshan Cao,1,2 Wen G Jiang,1 Lin Ye1 

1Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, Cardiff University School of Medicine, Academic Avenue, Cardiff, UK; 2Breast Cancer Centre, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China

Correspondence: Lin Ye, Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK, Tel +44 2920687861, Email YeL@Cardiff.ac.uk

Abstract: Breast cancer is one of the most common malignant tumours in women worldwide. A primary route for breast cancer cells to disseminate is through regional lymphatic vessels and nodes. Cancer cell-induced lymphangiogenesis plays a crucial role in lymphatic metastasis and is associated with poor survival of breast cancer. Advances in molecular biology have led to the identification of biomarkers associated with lymphangiogenesis and lymphatic metastasis, including lymphatic vessel endothelial cell (LVEC) markers and tumour microenvironment markers, such as vascular endothelial growth factor receptor 3 (VEGFR3), podoplanin (PDPN), and lymphatic endothelial hyaluronan receptor-1 (LYVE1). LVEC molecular markers play a profound role in both the formation of new lymphatic vessels and the invasive expansion of primary tumour. Abnormal expression of LVEC markers may contribute to lymphatic vessel disease and/or metastasis of cancer cells through the lymphatic system. These molecular markers may present a potential for targeted therapies and precision diagnostics for managing lymphatic metastasis in breast cancer. This review aims to provide a comprehensive summary of the current understanding of the molecular and cellular machinery underlying lymphatic metastasis in breast cancer, with a particular focus on the lymphangiogenic markers and their role in the lymphatic dissemination.

Keywords: lymph node metastasis, lymphangiogenesis, lymphatic vessel endothelial cell, biomarkers and breast cancer