Abstract
Abstract Abstract #1132 Background:
 Aromatase inhibitors (AIs) reduce circulating oestrogens and so should have either no or a positive effect on coagulation . This study compares the effects of the non-steroidal aromatase inhibitors, A and L and the steroidal inactivator, E on coagulation.
 Patients and Methods:
 This was an open, randomized pharmacodynamic study. Plasma coagulation factors were measured in 120 postmenopausal women with invasive ER +ve breast cancer. As part of their adjuvant hormone therapy, patients were randomized to receive upfront therapy with either:
 16 weeks of A, 16 weeks of L or 16 weeks of E.
 Fasting blood samples were collected at entry and after 12 and 16 weeks of each drug. AI patients were then switched to T and further samples measured after 8 months on T.
 Plasminogen activator inhibitor (PAI) antigen, von Willebrand's Factor (vWF) antigen, antithrombin III (AT111), protein C, protein S total, protein S free, activated protein C, resistance (APCR), factor VIII and fibrinogen were measured.
 Results:
 Results expressed as % change from baseline.
 E vs A vs L
 Protein C. E caused a significant fall compared to A and L (-15.75 (-21.48, -10.02) vs -3.80 (-10.77, 3.16) vs -3.63 (-10.50, 3.25)) respectively. p = 0.008.
 ATIII. E caused a significant fall from baseline (-8.55 (-13.33, -3.79))
 Protein S Free. E + A caused a significant increase from baseline (E 6.90 (1.98, 11.82), A 7.36 (1.37, 13.34).
 Steroidal vs non-steroidal:
 Protein C. A significantly greater fall was seen with E than A+L (-15.75 (-21.45, -10.05) vs -3.71 (-8.58, 1.15)) p = 0.002.
 vWF A+L caused a significant increase from baseline (6.52 (0.66, 12.38) but this was not statistically different to E 5.02 (-1.88, 11.91)).
 ATIII A significant decrease from baseline was seen with A + L, -4.54 (-8.64, -0.43) but no difference from E 8.55 (13.31, -3.70) p=0.21.
 Protein S Free There was a significant increase from baseline in both groups (A+L: 5.70 (1.47, 9.92), E: 6.90 (1.98, 11.81), but no difference between the groups p=0.72.
 T effect:
 AT111 and protein C levels fell significantly on T whereas protein S free increased on T. Prior A, E or L had no significant impact on post-tamoxifen results.
 Conclusions:
 No significant differences in any coagulation factors were seen between A and L
 E caused a significant fall in protein C and ATIII.
 The non-steroidal AIs caused a significant increase in vWF.
 T caused a significant fall in protein C and ATIII and a significant increase in protein S free.
 No AI significantly influenced post-tamoxifen results.
 These drugs have significant effects on coagulation which helps to explain their clinical effects on thrombotic and thromboembolic disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1132.
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