TUMOR ANGIOGENESIS IN NODE-NEGATIVE BREAST CARCINOMAS - RELATIONSHIP WITH EPIDERMAL GROWTH-FACTOR RECEPTOR, ESTROGEN-RECEPTOR, AND SURVIVAL

Angiogenesis is essential for tumor growth and metastases. Studies in breast carcinomas suggest that microvessel quantitation as a measure o f angiogenesis might be one of the most powerful prognostic tools avai lable. Node negative breast cancer is a particular group for which bet ter prognostic markers would be helpful. We therefore measured microve ssel density in a series of well characterised node negative breast ca rcinomas to evaluate angiogenesis as a prognostic marker and assess it s relationship to epidermal growth factor receptor (EGFR) and estrogen receptor (ER), which have previously been reported to be of value. 10 9 patients with a mean age of 55 years and a median follow-up of 25 mo nths were examined. Vessels were immunohistochemically highlighted usi ng an antibody to platelet endothelial cell adhesion molecule CD31, an d microvessel density was quantified using a Chalkley point eyepiece g raticule. No significant correlation was observed with patient age, tu mor size, grade, ER, or EGFR expression. In a univariate analysis of s urvival, whereas ER expression was not a significant indicator of eith er relapse-free (RFS) or overall survival (OS), vascular count (VC) pr edicted both early RFS and OS (p=0.01 and p=0.028 respectively). Furth ermore, in patients with ER positive tumors, a subgroup usually consid ered to have a good prognosis, there was a significant reduction in RF S and OS if tumors had high VCs (p=0.05 and p=0.002 respectively). A f urther statistically significant reduction in RFS (p=0.05) was observe d for EGFR positive highly vascular tumors. In a Cox proportional haza rd model, VC remained a significant prognostic indicator for both RFS and OS (p=0.04 and p=0.01) and conferred a 6.6 and 3.5 times respectiv e increased risk of mortality and relapse. These findings suggest that quantitation of angiogenesis is an independent predictor of survival in node negative breast carcinomas, and due to these high hazard ratio s might be more useful than other recently described prognostic marker s in selecting patients who would benefit from adjuvant therapy.