Vascular endothelial growth factor is associated with the efficacy of endocrine therapy in patients with advanced breast carcinoma

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Abstract
Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with a poor prognosis in patients with primary breast carcinoma. In the current study, the authors investigated whether there was an association between VEGF levels in tumor tissues and response rates to first-line, systemic therapy in patients with advanced breast carcinoma. In 172 tumors from patients with primary breast carcinoma who developed distant metastases during follow-up, cytosolic levels of VEGF were measured using a quantitative enzyme-linked immunosorbent assay. Patients received either endocrine therapy (n = 96) or chemotherapy (n = 76) as first-line treatment after they were diagnosed with advanced disease. In univariate logistic regression analysis for response to endocrine therapy in 96 patients, an increasing level of VEGF, as a log-transformed, continuous variable, was correlated with a poor rate of response (P = 0.043). In multivariate analysis, a significantly lower rate of response to first-line endocrine therapy was found for patients who had high VEGF levels compared with patients who had low VEGF levels (P = 0.025). Similar results were found for the subgroup of 82 patients who received tamoxifen (P = 0.011). An association of VEGF with response to first-line endocrine therapy was found in addition to a predictive impact for estrogen receptor/progesterone receptor status (P = 0.027). VEGF levels did not predict the rate of response to first-line chemotherapy. The results demonstrated that the level of VEGF affects response to endocrine therapy independent of steroid hormone receptor status and may help to refine further the indication for this treatment in individual patients. Further studies are warranted to explain this underlying resistance to endocrine therapy.