Association of eNOS polymorphisms with clinical outcome in bevacizumab-treated breast cancer patients.

e22075 Background: VEGF overproduction induces angiogenesis and up-regulates endothelial nitric oxide synthase (eNOS) resulting in endothelial barrier disruption, edema and impaired tumor drug delivery (Goel S et al. Physiol Rev 2011;91:1071). The eNOS gene variants c.-786C>T and c.894G>T are associated with reduced NO production and higher incidence of hypertension (HT) (Niu W, Qi Y. PLoS One 2011;6:e24266). Since suppression of VEGF-eNOS axis may normalize interstitial pressure and enhance tumor drug delivery, but may induce HT, this study examined the association between major eNOS variants c.-786C>T and c.894G>T with treatment outcome and risk of HT in metastatic breast cancer (MBC) patients receiving bevacizumab. Methods: MBC subjects (n=75) were enrolled; main characteristics were: mean age 49.5 yrs (range 29-73) at first diagnosis, 53 yrs (range 34-74) at metastatic progression and PS 0-1. Four subjects with HT and 1 patient with compensated cardiovascular disease were also included; 24 subjects ha...