EFFECT OF ANTIESTROGEN REGIMEN ON PROSTACYCLIN AND THROMBOXANE A(2) IN POSTMENOPAUSAL PATIENTS WITH BREAST-CANCER - EVIDENCE OF SIGNIFICANCE OF HYPERTENSION, SMOKING OR PREVIOUS USE OF ESTROGEN THERAPY

To explore the mechanism(s) by which antiestrogens may protect against the development of cardiovascular disorders, we measured the producti on 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 assa yed by high performance liquid chromatography and radio-immunoassays f or 2,3-dinor-6-ketoprostaglandin F1 alpha (=metabolite of PGI(2), dino r-6-keto) and for 2,3-dinor-thromboxane B-2 (=metabolite of TxA(2), di nor-TxB(2)). In addition, in 35 of these 38 patients we assayed the ca pacity of platelets to produce thromboxane A(2) during standardized bl ood clotting. The 4 patients using low-dose aspirin had low thromboxan e production, and were excluded from further analysis of the data. An antiestrogen regimen consisting either of tamoxifen (n = 15) or of tor emifene (n = 19) caused no changes in production of PGI(2) or TxA(2), dr in their ratio, and in this regard, these antiestrogens behaved sim ilarly. 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 < 0.05) and red uced platelet capacity to produce TxA(2) (62.6 +/- 67.8 vs 134.6 +/- 7 5,6 ng/mL, p < 0.05). The patients (n = 15) who had used estrogen repl acement therapy (ERT) up until diagnosis of breast cancer showed reduc ed dinor-TxB(2) excretion (15.5 +/- 12.7 vs 29.9 +/- 20.9 ng/mmol, p < 0.05) before initiation of antiestrogens, and elevated dinor-6-keto o utput during the antiestrogen regimen (32.4 +/- 21.2 vs 22.7 +/- 8.7 n g/mmol, p = 0.07). Smokers (n = 6) had elevated dinor-TxB(2) output be fore and during antiestrogen use. Thus we conclude that the cardiovasc ular prosection provided by an antiestrogen regimen is unlikely to be mediated through vaso- and platelet active PGI(2) and TxA(2).