他莫昔芬和芳香化酶抑制剂对乳腺癌女性患者血管内皮生长因子和内皮抑素水平的影响存在差异。

Tamoxifen and aromatase inhibitors differentially affect vascular endothelial growth factor and endostatin levels in women with breast cancer.

作者信息

Holmes Chris E, Huang Joe C, Pace Thomas R, Howard Alan B, Muss Hyman B

机构信息

Department of Medicine, University of Vermont, Burlington, Vermont, USA.

出版信息

Clin Cancer Res. 2008 May 15;14(10):3070-6. doi: 10.1158/1078-0432.CCR-07-4640.

DOI:10.1158/1078-0432.CCR-07-4640

PMID:18483373

Abstract

PURPOSE

Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation).

EXPERIMENTAL DESIGN

VEGF and endostatin concentrations were measured with a quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women with breast cancer treated with either tamoxifen (n = 14) or aromatase inhibitors (n = 16). Platelet activation was induced by a thrombin receptor agonist.

RESULTS

Tamoxifen therapy resulted in an increase in platelet releasate concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P = 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen therapy resulted in no change in serum or plasma endostatin concentrations. Platelet releasate concentrations of endostatin did not change with either treatment. Interindividual variability was noted among both aromatase inhibitor--and tamoxifen-treated patients.

CONCLUSIONS

Tamoxifen and aromatase inhibitor therapy affect VEGF and endostatin levels and likely contribute to the angiogenic balance in breast cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer.

摘要

目的

循环及细胞中的促血管生成和抗血管生成蛋白，如血管内皮生长因子（VEGF）和内皮抑素，参与局部血管生成平衡的调节。我们探讨了他莫昔芬和芳香化酶抑制剂对血浆、血清及血小板释放物（由血小板激活诱导产生）中VEGF和内皮抑素浓度的影响。

实验设计

对30例接受他莫昔芬（n = 14）或芳香化酶抑制剂（n = 16）治疗的乳腺癌女性患者，在治疗1至5周前后，采用定量免疫分析法测定VEGF和内皮抑素浓度。通过凝血酶受体激动剂诱导血小板激活。

结果

他莫昔芬治疗导致血小板释放物中VEGF浓度升高（P = 0.01），但血浆VEGF无变化。相比之下，芳香化酶抑制剂治疗不影响血清、血浆或血小板释放物中的VEGF。单因素分析显示，使用阿司匹林可减弱他莫昔芬相关的血小板释放物中VEGF的升高，并降低血清VEGF水平（P = 0.03）。芳香化酶抑制剂治疗导致血清内皮抑素浓度降低（P = 0.04），而在使用芳香化酶抑制剂治疗期间，血浆内皮抑素浓度有升高趋势（P = 0.06）。他莫昔芬治疗导致血清或血浆内皮抑素浓度无变化。两种治疗方法均未使血小板释放物中的内皮抑素浓度发生改变。在接受芳香化酶抑制剂和他莫昔芬治疗的患者中均观察到个体间差异。