Effect of antiestrogen regimen on prostacyclin and thromboxane A2 in postmenopausal patients with breast cancer: Evidence of significance of hypertension, smoking or previous use of estrogen therapy

Abstract To explore the mechanism(s) by which antiestrogens may protect against the development of cardiovascular disorders, we measured the production of vasodilatory, antiaggregatory prostacyclin (PGI 2 and that of vasoconstrictive, proaggregatory thromboxane A 2 (TxA 2 ) before and after 6 months' use of antiestrogens in postmenopausal patients after operation for stage II breast cancer (n = 38). Urine samples were assayed by high performance liquid chromatography and radioimmunoassays for 2,3-dinor-6-ketoprostaglandin F1α (=metabolite of PGI 2 , dinor-6-keto) and for 2,3-dinor-thromboxane B 2 (=metabolite of TxA 2 , dinor-TxB 2 ). In addition, in 35 of these 38 patients we assayed the capacity of platelets to produce thromboxane A2 during standardized blood clotting. The 4 patients using low-dose aspirin had low thromboxane production, and were excluded from further analysis of the data. An antiestrogen regimen consisting either of tamoxifen (n = 15) or of toremifene (n = 19) caused no changes in production of PGI 2 or TxA 2 , or in their ratio, and in this regard, these antiestrogens behaved similarly. Hypertensive patients (n = 7) using different antihypertensive agents were characterized by reduced urinary out-put of dinor-6-keto (18.5 ± 6.1 vs 35.5 ± 18.5 ng/mmol, mean ± SD, p 2 (62.6 ± 67.8 vs 134.6 ± 75.6 ng/mL, p 2 excretion (15.5 ± 12.7 vs 29.9 ± 20.9 ng/mmol, p 2 and TxA 2 .