The Prognostic Value of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) and Associations to First Metastasis Site in 1307 Patients with Primary Breast Cancer
Barbro Kristina Linderholm, M.D. Karolinska Institute and Hospital, Stockholm, Sweden
Summary: Some breast cancer cells grown in vitro secrete large amounts of angiogenic factors known to contribute to tumor development and metastasis in vivo. These preliminary results suggest that high levels of the angiogenic factor called vascular endothelial growth factor (VEGF) secreted by primary breast cancer tumors may predict decreased survival in patients receiving adjuvant endocrine therapy. In contrast, high levels of the angiogenic factor called basic fibroblast growth factor (bFGF) were not predictive of survival.
Dr. Linderholm and colleagues are examining the angiogenic factors called vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as potential predictors of survival and sites of metastases in breast cancer.
Both VEGF and bFGF are known to promote tumor development and metastases. VEGF acts as a specific endothelial cell mitogen, induces proteolytic enzymes, and increases vascular permeability. The factor called bFGF has similar actions. Breast cancer cells from some patient tumors grown in vitro secrete large amounts of VEGF and bFGF, but the significance of this in the clinical setting is not known.
The researchers compared survival and sites of metastases in two groups of patients: Patients with primary breast tumors that secreted high levels of angiogenic factors in vitro and patients with tumors that secreted low levels when grown in vitro. A total of 1307 patients who had undergone surgery with axillary node dissection were included. The patients received adjuvant chemotherapy and/or endocrine therapy based on lymph node and hormone receptor status. Overall median survival was 70 months.
Dr. Barbro Linderholm reported that high levels of VEGF secreted by the primary tumor were found to be associated with negative steroid receptor status, presence of p53 mutations, and high histologic grade. In contrast, high levels of bFGF were associated with negative lymph node status and smaller tumors.
High levels of VEGF were also significantly associated both with lower overall survival and recurrence-free survival in patients who had received endocrine adjuvant therapy. Patients with tumors secreting high levels of VEGF also had increased rates of visceral and brain metastases compared with patients whose tumors secreted low levels of VEGF, but this difference was not statistically significant.
Although lower levels of bFGF tended to be associated with shorter overall survival and recurrence survival, the results were not significant.
Dr. Linderholm concluded that the predictive value of high levels of VEGF in primary breast tumors requires confirmation in a randomized trial.
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