Christine Stürken, Volker Möbus, Karin Milde-Langosch, Sabine Schmatloch, Peter Andreas Fasching, Josef Rüschoff, Elmar Stickeler, Rolf-Peter Henke, Carsten Michael Denkert, Lars Hanker, Christian Schem, Valentina A. Vladimirova, Thomas Karn, Valentina Nekljudova, Claus-Henning Köhne, Frederik Marmé, Udo Schumacher, Sibylle Loibl, Volkmar Müller
- Background: Breast cancer (BC) is the most frequent female cancer and preferentially metastasizes to bone. The transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism. However, it is not yet known whether TGIF is associated with BC bone metastasis or patient outcome and thus of potential interest. Methods: TGIF expression was analyzed by immunohistochemistry in 1197 formalin-fixed, paraffin-embedded tissue samples from BC patients treated in the GAIN (German Adjuvant Intergroup Node-Positive) study with two adjuvant dose-dense schedules of chemotherapy with or without bisphosphonate ibandronate. TGIF expression was categorized into negative/low and moderate/strong staining. Endpoints were disease-free survival (DFS), overall survival (OS) and time to primary bone metastasis as first site of relapse (TTPBM). Results: We found associations of higher TGIF protein expression with smaller tumor size (p= 0.015), well differentiated phenotype (p< 0.001) and estrogen receptor (ER)-positive BC (p< 0.001). Patients with higher TGIF expression levels showed a significantly longer disease-free (DFS: HR 0.75 [95%CI 0.59–0.95], log-rank p=0.019) and overall survival (OS: HR 0.69 [95%CI 0.50–0.94], log-rank p= 0.019), but no association with TTPBM (HR 0.77 [95%CI 0.51–1.16]; p= 0.213). Univariate analysis in molecular subgroups emphasized that elevated TGIF expression was prognostic for both DFS and OS in ER-positive BC patients (DFS: HR 0.68 [95%CI 0.51–0.91]; log-rank p= 0.009, interaction p= 0.130; OS: HR 0.60 [95%CI 0.41–0.88], log-rank p= 0.008, interaction p= 0.107) and in the HER2-negative subgroup (DFS:HR 0.67 [95%CI 0.50–0.88], log-rank p= 0.004, interaction p= 0.034; OS: HR 0.57 [95%CI 0.40–0.81], log-rank p= 0.002, interaction p= 0.015). Conclusions: Our results suggest that moderate to high TGIF expression is a common feature of breast cancer cells and that this is not associated with bone metastases as first site of relapse. However, a reduced expression is linked to tumor progression, especially in HER2-negative breast cancer.
MetadatenAuthor: | Christine Stürken, Volker MöbusGND, Karin Milde-Langosch, Sabine SchmatlochORCiDGND, Peter Andreas FaschingORCiDGND, Josef RüschoffGND, Elmar Stickeler, Rolf-Peter Henke, Carsten Michael Denkert, Lars HankerORCiDGND, Christian Schem, Valentina A. Vladimirova, Thomas Karn, Valentina Nekljudova, Claus-Henning Köhne, Frederik MarméORCiDGND, Udo Schumacher, Sibylle LoiblORCiDGND, Volkmar MüllerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-645665 |
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DOI: | https://doi.org/10.1186/s12885-021-08656-0 |
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ISSN: | 1471-2407 |
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Parent Title (English): | BMC cancer |
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Publisher: | BioMed Central |
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Place of publication: | London |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/08/14 |
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Date of first Publication: | 2021/08/14 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2022/03/10 |
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Tag: | Bone metastases; Breast cancer; TGFB-induced factor homeobox 1; TGIF |
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Volume: | 21 |
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Issue: | art. 920 |
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Page Number: | 11 |
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First Page: | 1 |
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Last Page: | 11 |
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Note: | The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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Note: | A Correction to this article was published on 15 September 2021. DOI 10.1186/s12885-021-08754-z |
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HeBIS-PPN: | 494568380 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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