The relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis

Purpose: The assessment of locally produced proangiogenic cytokines may be an indicator of the stromal response of an individual to wounding or cancer. This study describes the profile of VEGF production in human surgical wounds in both breast cancer patients and reduction mammoplasty controls, and assesses the changes in systemic VEGF levels and platelet profiles perioperatively. Experimental Design: Perioperative surgical wound fluid samples and blood were collected daily up to 13 days from 52 patients undergoing breast cancer surgery (local tumor burden), delayed breast reconstruction (previous tumor burden but none present at the time of surgery), or breast reduction surgery (noncancer control). Samples were analyzed for VEGF by ELISA Results: VEGF levels in surgical wound fluid were lowest on day 1 followed by an early peak on day 2 of >900% the corresponding serum value. There was a trend in the VEGF response at the day-2 time point: reduction > reconstruction > cancer subgroups, with a significant difference between the reduction and cancer subgroups (P <0.05). There was a 20-30-fold variation in the response between days 1 and 2, and within subgroups. Conclusions: Much higher local concentrations of angiogenic factors may need to be antagonized for effective antiangiogenic therapy, and there is great heterogeneity between patients. The small peripheral blood changes compared with large tumor fluid changes show that there is a tissue barrier. This has relevance for design of antiangiogenic therapy trials, highlighting the need for individually tailored treatment with biologically targeted interventions.