The Transcription Factor ZEB-1 Conveys Chemoresistance in Breast Cancer

Background: A transcription factor called zinc finger E-box binding homeobox 
1 (ZEB-1) controls tissue-specific processes and cell differentiation. In 
numerous human cancer types, including breast, pancreatic, osteosarcoma, lung, 
liver, gastric, colon, and uterine cancers, aberrant expression of ZEB-1 has been 
reported. The aim of this study was to assess the prognostic role of 
immunohistochemical expression of ZEB-1 transcription factor in breast cancer.
Material and method: This retrospective study investigated the prognostic 
role of immunohistochemical expression of ZEB-1 in breast cancer patients. It 
included 63 cases of newly diagnosed breast cancer patients, presented and 
diagnosed at South Egypt Cancer Institute, Assiut University between January 
2019 and December 2021. All patients were stained with anti ZEB-1 antibody. 
Patients followed up for at least 24 months.
Results: There was a significant association detected between high ZEB-1 
expression and poor response to the first line chemotherapy, development of 
metastasis (P value <0.001) {42.2% of patients with high ZEB-1 expression 
progressed with newly developed distant metastasis after receiving adjuvant 
treatment } and disease progression especially disease progression with bone 
metastasis in the studied breast cancer cases (P value= 0.006 as six cases with
high ZEB-1 expression progressed with newly developed bone metastasis after 
receiving adjuvant treatment }. There was a significant association detected 
between low ZEB-1 expression and increased disease free survival (P value= 
0.001 as 92% of patients with low ZEB-1 expression were disease free during 
the whole period of follow up). There was a significant association detected 
between diagnosis with advanced tumor stage and decreased disease free 
survival (P value=0.023) and also with decreased overall survival (P 
value=0.042) of the studied breast cancer cases. There was a significant 
association detected between diagnosis with multicenteric tumor type &/or 
presence of Paget`s disease and decreased overall survival of the studied breast 
cancer cases with (P value =0.018) and (P value=0.014) respectively as patients 
with multicenteric tumor &/or patients with paget’s disease shown to have 
decreased overall survival when compared with patients with unicenteric tumor 
&/or patients without paget’s disease. However, there was no significant 
association found between high ZEB-1 expression and clinicopathological data, 
hormonal profile or overall survival (P value=0.009) of the studied breast cancer 
cases. 
Conclusions: High ZEB-1 protein expression was a poor predictive marker of 
disease-free survival in breast cancer patients (P value=0.001). Also, there was a 
pivotal role of high ZEB-1 expression in disease progression and development 
of metastasis (P value<0.001) especially progression with bone metastasis 
among breast cancer patients (P value=0.006).