Abstract
A recent meta-analysis indicated that higher tumoral expression of vascular endothelial growth factor C (VEGF-C) was related to poorer relapse-free and overall survival in breast cancer patients. However, a retrospective study found that higher circulating VEGF-C levels were associated with better survival in breast cancer patients. In 2009, we initiated a prospective study to determine the utility of preoperative serum VEGF-C levels for predicting the risk of sentinel lymph node involvement in early breast cancer and to assess serum VEGF-C levels as a prognostic factor for relapse-free and overall survival. We analyzed serum samples from 174 patients with early breast cancer who underwent sentinel lymph node biopsies. VEGF-C levels were determined using an ELISA. Serum VEGF-C levels were normally distributed, with a median value of 6561.5 pg/mL, and did not correlate with any other clinical or pathological variables. During a median follow-up period of 58 months, the five-year relapse-free survival rate was higher in patients with VEGF-C levels above the median than in patients with lower levels (95.3% vs. 85.9%, p < 0.04). No association was found between VEGF-C levels and overall survival. Our study demonstrates that the prognosis was better for early breast cancer patients with high serum VEGF-C levels.
Highlights
The invasion of solid tumors into the lymph vessels and the consequent generation of lymph node metastases require the growth of new lymphatic vessels
Our study demonstrates that the prognosis was better for early breast cancer patients with high serum vascular endothelial growth factor C (VEGF-C) levels
Axillary lymph node metastasis is the main predictor of survival in patients with operable breast cancer
Summary
The invasion of solid tumors into the lymph vessels and the consequent generation of lymph node metastases require the growth of new lymphatic vessels (lymphangiogenesis). The expression of VEGF-C (and to a lesser extent that of VEGF-D) has been shown to correlate strongly with the risk of lymph node metastasis in over 30 studies of different malignancies, including lung, breast and colon cancers [2,3,4]. A recent meta-analysis that included 21 studies and 2828 patients with breast cancer reported hazard ratios (HRs) of 1.87 (95% confidence interval [CI] 1.25–2.79, p = 0.001) for RFS and 1.96 (95% CI 1.15–3.31, p = 0.001) for OS in patients with high tumor VEGF-C expression [5]. The cut-off values used to define high tumor VEGF-C expression varied considerably among the studies
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