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- Title
TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer.
- Authors
Stürken, Christine; Möbus, Volker; Milde-Langosch, Karin; Schmatloch, Sabine; Fasching, Peter A.; Rüschoff, Josef; Stickeler, Elmar; Henke, Rolf-Peter; Denkert, Carsten; Hanker, Lars; Schem, Christian; Vladimirova, Valentina; Karn, Thomas; Nekljudova, Valentina; Köhne, Claus-Henning; Marmé, Frederik; Schumacher, Udo; Loibl, Sibylle; Müller, Volkmar
- Abstract
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.
- Subjects
BREAST cancer; OVERALL survival; HORMONE receptor positive breast cancer; CANCER relapse; BONE metastasis; ESTROGEN receptors; PROGRESSION-free survival
- Publication
BMC Cancer, 2021, Vol 21, Issue 1, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/s12885-021-08656-0