Tamoxifen treatment of metastatic breast cancer and antithrombin III levels

Abstract

Reported in the literature are several cases of thromboembolic complications occurring in patients on tamoxifen citrate for metastatic breast cancer. In view of this literature, a study of patients on tamoxifen was initiated to determine if a paradoxical estrogenic effect was present as evidenced by lowered levels of antithrombin III (AT III). Both functional and immunologic levels were assayed. Twenty-four women with metastatic breast cancer (predominantly bone, 83%) on tamoxifen 10 mg by mouth twice daily were studied. The mean duration of tamoxifen therapy at the time of the AT III determination was 36 weeks (range, 2-87 weeks). The mean age of the group was 64 years with a mean functional AT III of 86% (normal, 82%-120%). Ten of 24 (42%) had low levels of functional AT III (mean, 75%), whereas, the remaining 14 (58%) had normal levels of functional AT III (mean, 94%). Immunologic AT III levels were normal in 23 patients (mean, 26 mg/dl; normal range, 17-30 mg/dl) and elevated in 1 patient. Similarly, functional and immunologic AT III levels were determined in 11 women with metastatic breast cancer on no hormonal therapy. One of 11 (9%) had a low level of functional AT III with a mean of 102% for the entire group. The mean immunologic AT III was 28 mg/dl with two elevated. The poor correlation between functional and immunologic AT III levels may be similar to the disparity noted in women using estrogen-containing oral contraceptives. The finding of lowered functional activity of AT III in 42% of tamoxifen-treated patients is preliminary in nature and will require larger confirmatory studies, including further clinical correlation of this observation.