Göbel Andy, Kuhlmann Jan D, Link Theresa, Wimberger Pauline, Browne Andrew J, Rauner Martina, Hofbauer Lorenz C, Rachner Tilman D
Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, TU Dresden Medical Center, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
German Cancer Consortium (DKTK), Partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Breast Cancer Res Treat. 2017 Aug;164(3):737-743. doi: 10.1007/s10549-017-4296-3. Epub 2017 May 19.
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 ± 14.6 and 27.1 ± 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.
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不可或缺。他莫昔芬在骨骼中表现出部分ER激动作用，而芳香化酶抑制剂会增加骨吸收和骨折风险。Wnt抑制剂Dickkopf-1（DKK-1）和硬化蛋白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和硬化蛋白水平的影响仍不明确。
在一组45例接受辅助他莫昔芬或芳香化酶抑制剂治疗的绝经前和绝经后原发性雌激素受体阳性乳腺癌女性患者中，于初次诊断时以及术后3 - 5天和12个月测量血清DKK-1和硬化蛋白水平。
DKK-1和硬化蛋白的平均基线水平±标准差分别为29.7±14.6和27.1±16.2 pmol/l。观察到DKK-1水平与年龄呈显著负相关（r = -0.32；p < 0.05），而硬化蛋白则无此相关性。值得注意的是，围绝经期和绝经后女性的DKK-1水平显著低于绝经前患者（-47%；p < 0.05）。在接受他莫昔芬治疗的患者中，术后一年DKK-1水平降低了35%（p < 0.01），但接受芳香化酶抑制剂治疗的患者中该水平未改变。硬化蛋白未观察到显著变化。
接受他莫昔芬辅助治疗的乳腺癌患者血清DKK-1水平降低，这可能有助于其骨保护特性。
