Tamoxifen-Induced Changes in the Plasma Fibrinolytic Factors in Menopausal Women with Breast Cancer

There is evidence that tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and the plasminogen activator inhibitors 1 and 2 (PAI-1, PAI-2), are involved in the invasion and metastasis of breast tumors. Menopausal controls and menopausal women with breast cancer, who were taking tamoxifen, 10 mg b.i.d., had plasma antigenic levels of tPA, uPA, PAI-1, and PAI-2 determined by enzyme-linked immunosorbent assay (ELISA). In addition, five women being placed on this tamoxifen regimen also had these same determinations made before 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-1. Nonsignificant increases were also seen in the five women evaluated before and after initiation of treatment. Linear correlations were seen for tPA and PAI-1 over time length of exposure to tamoxifen. Ratios of tPA/PAI- 1 and UPA/PAI-1 were not significantly different, but were correlated and linear. From these data, it appears that tamoxifen increases the fibrinolytic factors in these patients and that this was not proportional as the ratios of the factors were not different after treatment. The increase in activators was greater than inhibitors, which could be detrimental in terms of the potential for invasion and metastasis of the tumor cell. As a negative correlation was seen for tPA over time while PAI- was positively correlated, this may help explain why some patients taking tamoxifen are at risk for thromboembolytic events. Key Words: TPA—uPA—PAI-1—PAI-2—Tamoxifen—Breast cancer.