PURPOSE: Circulating and cellular proangiogenic and antiangiogenic proteins such 
as vascular endothelial growth factor (VEGF) and endostatin contribute to the 
local angiogenic balance. We explored the effects of tamoxifen and aromatase 
inhibitors on concentrations of VEGF and endostatin in plasma, serum, and 
platelet releasate (induced by platelet activation).
EXPERIMENTAL DESIGN: VEGF and endostatin concentrations were measured with a 
quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women 
with breast cancer treated with either tamoxifen (n = 14) or aromatase 
inhibitors (n = 16). Platelet activation was induced by a thrombin receptor 
agonist.
RESULTS: Tamoxifen therapy resulted in an increase in platelet releasate 
concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, 
aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate 
VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated 
increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P 
= 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin 
concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to 
be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen 
therapy resulted in no change in serum or plasma endostatin concentrations. 
Platelet releasate concentrations of endostatin did not change with either 
treatment. Interindividual variability was noted among both aromatase 
inhibitor--and tamoxifen-treated patients.
CONCLUSIONS: Tamoxifen and aromatase inhibitor therapy affect VEGF and 
endostatin levels and likely contribute to the angiogenic balance in breast 
cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, 
suggesting that antiplatelet and/or antiangiogenic therapy might improve the 
effectiveness of tamoxifen in women with breast cancer.