Adjuvant tamoxifen but not aromatase inhibitor therapy decreases serum levels of the Wnt inhibitor dickkopf-1 while not affecting sclerostin in breast cancer patients
Adjuvant tamoxifen but not aromatase inhibitor therapy decreases serum levels of the Wnt inhibitor dickkopf-1 while not affecting sclerostin in breast cancer patients
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DOI：
10.1007/s10549-017-4296-3
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发表时间：
2017-08-01
影响因子：
3.8
通讯作者：
Rachner, Tilman D.
中科院分区：
文献类型：
--
作者：
Goebel, Andy;Kuhlmann, Jan D.;Rachner, Tilman D.
内分泌治疗，包括他莫昔芬或芳香化酶抑制剂，对于雌激素受体（ER）和/或孕激素阳性乳腺癌患者的治疗是必不可少的。虽然他莫昔芬在骨中显示部分内质网激动作用，但芳香化酶抑制剂增加骨吸收和骨折风险。Wnt抑制剂dickkopf-1 （DKK-1）和sclerostin对骨形成有负面影响，被认为是治疗骨疾病的靶点。然而，内分泌治疗对原发性乳腺癌患者血清DKK-1和硬化素水平的影响尚不清楚。在一组45名绝经前和绝经后原发性雌激素受体阳性乳腺癌患者中，经辅助治疗他莫昔芬或芳香酶抑制剂后，在原发性诊断时以及术后3-5天和12个月测量血清DKK-1和硬化蛋白水平。DKK-1和sclerostin的平均基线水平+/- SD分别为29.7 +/- A 14.6和27.1 +/- A 16.2 pmol/l。DKK-1水平与年龄呈显著负相关（r = -0.32; p < 0.05），但与硬化蛋白无关。值得注意的是，与绝经前患者相比，围绝经期和绝经后妇女的DKK-1水平显著降低（-47%;p < 0.05）。在他莫昔芬治疗的患者中，DKK-1水平在手术一年后降低了35% (p < 0.01)，但在芳香酶抑制剂治疗的患者中保持不变。硬化蛋白未见明显变化。在接受他莫昔芬辅助治疗的乳腺癌患者中，DKK-1血清水平降低，可能有助于其骨骼保护特性。
Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive.Serum DKK-1 and sclerostin levels were measured at primary diagnosis as well as 3-5 days and 12 months after surgery in a cohort of 45 pre- and postmenopausal women with primary estrogen receptor-positive breast cancer treated with adjuvant tamoxifen or aromatase inhibitors.Mean baseline levels +/- SD for DKK-1 and sclerostin were 29.7 +/- A 14.6 and 27.1 +/- A 16.2 pmol/l, respectively. A significant negative correlation of DKK-1 levels and age was observed (r = -0.32; p < 0.05), but not for sclerostin. Of note, DKK-1 levels were significantly lower in peri- and postmenopausal women compared to premenopausal patients (-47%; p < 0.05). In tamoxifen-treated patients, DKK-1 levels were reduced by 35% (p < 0.01) one year after surgery but remained unaltered in patients treated with aromatase inhibitors. No significant changes were observed for sclerostin.DKK-1 serum levels were reduced in breast cancer patients receiving an adjuvant therapy with tamoxifen, possibly contributing to its bone-protective properties.