TAMOXIFEN-INDUCED CHANGES IN THE PLASMA FIBRINOLYTIC FACTORS IN MENOPAUSAL WOMEN WITH BREAST-CANCER

There is evidence that tissue-type plasminogen activator (tPA), urokin ase-type plasminogen activator (uPA), and the plasminogen activator in hibitors 1 and 2 (PAI-1, PAI-2), are involved in the invasion and meta stasis of breast tumors. Menopausal controls and menopausal women with breast cancer, who were taking tamoxifen, 10 mg b.i.d., had plasma an tigenic levels of tPA, uPA, PAI-1, and PAI-2 determined by enzyme-link ed immunosorbent assay (ELISA). In addition, five women being placed o n this tamoxifen regimen also had these same determinations made befor e and after 6 months. Significant increases were observed for tPA, uPA , and PAI-1 in the 26 tamoxifen-treated patients. The percent increase in tPA and uPA combined were greater than that of PAI-I. Nonsignifica nt increases were also seen in the five women evaluated before and aft er initiation of treatment. Linear correlations were seen for tPA and PAI-1 over time length of exposure to tamoxifen. Ratios of tPA/PAI-1 a nd uPA/PAI-1 were not significantly different, but were correlated and linear. From these data, it appears that tamoxifen increases the fibr inolytic factors in these patients and that this was not proportional as the ratios of the factors were not different after treatment. The i ncrease in activators was greater than inhibitors, which could be detr imental in terms of the potential for invasion and metastasis of the t umor cell. As a negative correlation was seen for tPA over time while PAI-1 was positively correlated, this may help explain why some patien ts taking tamoxifen are at risk for thromboembolytic events.