The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis

Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.