High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer

Vascular endothelial growth factor (VEGF), a potent angiogenic factor, has been reported to be associated with a poor prognosis in primary breast canc er and in several other cancer types. In the present study, we have measure d with ELISA the levels of VEGF in cytosolic extracts of 815 primary breast tumors of patients who developed a recurrence during follow-up. All of the patients received tamoxifen (n = 618) or cyclophosphamide, methotrexate, 5 -fluorouracil (CMF) or 5-fluorouracil, Adriamycin, cyclophosphamide (FAC) c hemotherapy (n = 227) as first-line systemic therapy after diagnosis of adv anced disease. VEGF levels were not related to age or menopausal status but were negatively related to the cytosolic levels of estrogen receptor and p rogesterone receptor (P < 0.0001). In patients who relapsed within 1 year a fter primary surgery, tumor VEGF levels were higher than in patients who sh owed a longer disease-free interval (P = 0.0005), In patients with a First relapse in the viscera, VEGF levels were higher compared with those that re lapsed to the bone or soft tissue (P = 0.0004). In univariate analysis For response to first-line tamoxifen therapy, patients with high or intermediat e levels showed a poor rate of response, compared with patients with low tu mor-VEGF levels (P = 0.0001), Similarly, in multivariate analysis for respo nse to tamoxifen treatment, corrected for age, site of relapse, disease-fre e interval, and estrogen receptor and progesterone receptor status, VEGF st atus was an independent predictive factor (P = 0.009), In concordance, high er levels of VEGF were associated with a short progression-free survival an d postrelapse overall survival (both, P < 0.0001). On first-line chemothera py, the rate of response decreased with higher tumor levels of VEGF, both i n univariate (P = 0.003) and in multivariate analysis (P = 0.004), Furtherm ore, higher VEGF levels were associated with a short progression-free survi val (P = 0.003) and postrelapse overall survival (P = 0.001), In conclusion , the tumor VEGF level is an important independent marker that predicts a p oor efficacy of both tamoxifen and chemotherapy in advanced breast cancer, Know-ledge of the tumor level of VEGF might be helpful in selecting individ ual patients who may benefit from treatments with antiangiogenic agents com bined with conventionally used drugs.