Wege, Anja Kathrin and Chittka, Dominik and Buchholz, Stefan and Klinkhammer-Schalke, Monika and Diermeier-Daucher, Simone and Zeman, Florian and Ortmann, Olaf and Brockhoff, Gero (2018) HER4 expression in estrogen receptor-positive breast cancer is associated with decreased sensitivity to tamoxifen treatment and reduced overall survival of postmenopausal women. BREAST CANCER RESEARCH, 20: 139. ISSN 1465-542X, 1465-5411
Full text not available from this repository. (Request a copy)Abstract
BackgroundThe sensitivity of estrogen receptor-positive breast cancers to tamoxifen treatment varies considerably, and the molecular mechanisms affecting the response rates are manifold. The human epidermal growth factor receptor-related receptor HER2 is known to trigger intracellular signaling cascades that modulate the activity of coregulators of the estrogen receptor which, in turn, reduces the cell sensitivity to tamoxifen treatment. However, the impact of HER2-related receptor tyrosine kinases HER1, HER3, and, in particular, HER4 on endocrine treatment is largely unknown.MethodsHere, we retrospectively evaluated the importance of HER4 expression on the outcome of tamoxifen- and aromatase inhibitor-treated estrogen receptor-positive breast cancer patients (n=258). In addition, we experimentally analyzed the efficiency of tamoxifen treatment as a function of HER4 co-expression in vitro.ResultsWe found a significantly improved survival in tamoxifen-treated postmenopausal breast cancer patients in the absence of HER4 compared with those with pronounced HER4 expression. In accordance with this finding, the sensitivity to tamoxifen treatment of estrogen and HER4 receptor-positive ZR-75-1 breast cancer cells can be significantly enhanced by HER4 knockdown.ConclusionWe suggest an HER4/estrogen receptor interaction that impedes tamoxifen binding to the estrogen receptor and reduces treatment efficiency. Whether the sensitivity to tamoxifen treatment can be enhanced by anti-HER4 targeting needs to be prospectively evaluated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MEDIATES ACQUIRED-RESISTANCE; ENDOCRINE THERAPY; CROSS-TALK; IN-SITU; GROWTH; ERBB4; TRASTUZUMAB; MECHANISMS; PROTEIN; COEXPRESSION; HER4 receptor; Estrogen receptor positive breast cancer; Tamoxifen treatment |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Oct 2019 06:38 |
| Last Modified: | 09 Oct 2019 06:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13530 |
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