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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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.
KeywordsBreast cancer Dickkopf-1 Sclerostin Tamoxifen Aromatase inhibitors
The authors would like to thank Ms. Franziska Paul and Ms. Josefa Hötzel for their excellent technical assistance and Ms. Theresa Reiche for her secretarial assistance. The work was funded by the Deutsche Forschungsgemeinschaft to TDR (RA 2151/2-1, 2-2, and 3-1), MR (RA 1923/5-1), and to LCH (HO 1875/15-1 and 16-1) as part of the DFG Research group SKELMET.
Study Design: AG and TDR. Study conduct: AG, JDK, TL, and AJB. Data collection: AG, JDK, TL. Data analysis: AG, JDK, and TDR. Data interpretation: AG, JDK, PW, AJB, MR, LCH, and TDR. Drafting Manuscript: AG and TDR. Revising manuscript content: AG, JDK, TL, PW, AJB, MR, LCH, and TDR. Approving final version of manuscript: AG, JDK, TL, PW, AJB, MR, LCH, and TDR. AG takes responsibility for the integrity of the data analysis.
Compliance with ethical standards
Conflict of interest
The authors have received grants or honorarium for advisory boards or lectures to the individual or the institution by Amgen (LCH, TDR, TL, and PW), AstraZeneca (PW), Celgene (PW), Pfizer (PW), Lilly (LCH), Alexion (LCH), UCB (LCH), Novartis (PW, TL), Merck (LCH, TDR), PharmaMar (PW), Roche (PW) and TEVA (PW). AG, JDK, AJB, and MR declare no conflict of interest.
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