Abstract P1-08-32: Endothelin-1 genetic polymorphism as predictive marker for bevacizumab in metastatic breast cancer

Abstract Background: Biomarkers predicting response or toxicity of bevacizumab containing therapy in breast cancer are of urgent need. The genetic variability of VEGF, its receptor or other genes involved in angiogenesis could explain the inter-patient variability of drug effects and treatment resistance. Patients and methods: DNA was extracted from 180 paraffin-embedded tumor tissue blocks of patients with locally advanced or metastatic breast cancer treated with bevacizumab in combination with chemotherapy at our institution. We assessed the correlation of 11 SNPs in VEGF-A, VEGFR-1, STK39, endothelin-1 and uromodulin with outcome and toxicity. Results: Only one SNP in endothelin-1 (rs5370 TT) was significantly associated with worse median progression-free survival (HR 2.13, 95% CI 1.04 to 4.35, P = .038) and median overall survival (HR 2.88, 95% CI 1.40 to 5.93, P = .0042) compared with the alternate genotypes combined. One VEGF genotype (VEGF-634 GG) was associated with a significantly higher rate of treatment-induced hypertension when compared with the alternate genotypes combined (P = .048). Conclusion: Although these data need to be confirmed in larger trials, germline polymorphisms could help identifying patients who do not gain any benefit from anti-VEGF agents or who are at high risk of toxicity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-32.