Journal Article

TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer

Rüschoff, Josef, Köhne, Claus-Henning, Denkert, Carsten, Karn, Thomas, Milde-Langosch, Karin, Hanker, Lars, Loibl, Sibylle, Müller, Volkmar, Fasching, Peter A., Möbus, Volker, Nekljudova, Valentina, Marmé, Frederik, Schmatloch, Sabine, Schem, Christian, Henke, Rolf-Peter, Stürken, Christine, Vladimirova, Valentina, Schumacher, Udo, Stickeler, Elmar

2021

Overview

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. Trial registration This clinical trial has been registered with ClinicalTrials.gov ; registration number: NCT00196872 .

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antibodies / Biomedical and Life Sciences / Biomedicine / Bisphosphonates / Bone metastases / Bone turnover / Breast cancer / Cancer Research / Chemotherapy / Development and progression / ErbB-2 protein / Estrogen receptors / Genetic aspects / Health aspects / Health Promotion and Disease Prevention / Homeobox / Ibandronic acid / Immunohistochemistry / Laboratories / Lymphatic system / Medical prognosis / Medicine/Public Health / Metastases / Metastasis / Oncology / Paraffin / Patients / Phenotypes / Physiological aspects / Protein expression / Proteins / Surgical Oncology / TGFB-induced factor homeobox 1 / TGIF / Transcription factors / Womens health