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Correlation of Vascular Endothelial Growth Factor Content With Recurrences, Survival, and First Relapse Site in Primary Node-Positive Breast Carcinoma After Adjuvant Treatment

From the Departments of Oncology and Clinical Chemistry, Umeå University, Umeå, Sweden.

Address reprint requests to Barbro Linderholm, MD, Department of Oncology, Umeå University, SE-901 85 Umeå, Sweden; email barbro.linderholm{at}onkologi.umu.se

PURPOSE: To determine the predictive value of vascular endothelial growth factor (VEGF) for relapse-free survival (RFS) and overall survival (OS) in primary node-positive breast cancer (NPBC) after adjuvant endocrine treatment or adjuvant chemotherapy.

MATERIALS AND METHODS: VEGF was quantitatively measured in tumor cytosols from 362 consecutive patients with primary NPBC using an enzyme immunoassay for human VEGF₁₆₅. Adjuvant treatment was given to all patients, either as endocrine therapy (n = 250) or chemotherapy (n = 112). The median follow-up time was 56 months.

RESULTS: Univariate analysis showed VEGF to be a significant predictor of RFS (P = .0289) and OS (P = .0004) in the total patient population and in patients who received adjuvant endocrine treatment (RFS, P = .0238; OS, P = .0121). In the group of patients who received adjuvant chemotherapy, no significant difference was seen in RFS, but a difference was seen in OS (P = .0235). Patients with bone recurrences tended to have lower VEGF expression (median, 2.17 pg/µg DNA) than patients with visceral metastasis (4.41 pg/µg), brain metastasis (8.29 pg/µg), or soft tissue recurrences (3.16 pg/µg). Multivariate analysis showed nodal status (P = .0004), estrogen receptor (ER) status (P < .0001), and tumor size (P = .0085) to be independent predictors of RFS. VEGF was found to be an independent predictor of OS (P = .0170; relative risk [RR] = 1.82), as were ER (P < .0001; RR = 5.19) and nodal status (P = .0002; RR = 2.58). For patients receiving adjuvant endocrine treatment, multivariate analysis showed VEGF content to be an independent predictor of OS (P = .0420; RR = 1.90) but not of RFS.

CONCLUSION: The results suggest that VEGF₁₆₅ content in tumor cytosols is a predictor of RFS and OS in primary NPBC. VEGF content might also predict outcome after adjuvant endocrine treatment, but further studies in a prospective setting with homologous treatments are required.

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