TY  - JOUR
A1  - Stürken, Christine
A1  - Möbus, Volker
A1  - Milde-Langosch, Karin
A1  - Schmatloch, Sabine
A1  - Fasching, Peter Andreas
A1  - Rüschoff, Josef
A1  - Stickeler, Elmar
A1  - Henke, Rolf-Peter
A1  - Denkert, Carsten Michael
A1  - Hanker, Lars
A1  - Schem, Christian
A1  - Vladimirova, Valentina A.
A1  - Karn, Thomas
A1  - Nekljudova, Valentina
A1  - Köhne, Claus-Henning
A1  - Marmé, Frederik
A1  - Schumacher, Udo
A1  - Loibl, Sibylle
A1  - Müller, Volkmar
T1  - TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer
T2  - BMC cancer
N2  - 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.
KW  - Breast cancer
KW  - TGFB-induced factor homeobox 1
KW  - TGIF
KW  - Bone metastases
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/64566
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-645665
SN  - 1471-2407
N1  - 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.
N1  - A Correction to this article was published on 15 September 2021. DOI 10.1186/s12885-021-08754-z
VL  - 21
IS  - art. 920
SP  - 1
EP  - 11
PB  - BioMed Central
CY  - London
ER  -