TGF-β signaling is highly important in tumor growth and progression, however, the value of TGF-β family proteins as potential resistance-related markers is not fully understood, especially in breast cancer molecular subtypes. The aim of this study was to examine the contribution of TGF-β family proteins to tamoxifen response in luminal breast cancer patients with different HER2 phenotypes.
TGF-β, TGF-βRI, TGF-βRII and ERα mRNA and protein expression levels were quantified using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in 60 tissue specimens from breast cancer patients with luminal B HER2 negative and luminal HER2 positive phenotype. Flow cytometry was used to evaluate the co-expression of TGF-βRI and CD24 in breast cancer tissue. Association analysis of progression-free survival (PFS) with selected markers was conducted using Kaplan-Meier plots and log-rank test. Tamoxifen resistance was defined as clinical progression during disease treatment or relapse.
High mRNA expression of ESR1 as well as homogeneous ERα expression in tumor were significantly related to favorable tamoxifen response in luminal B breast cancer patients with HER2-negative phenotype (р = 0.046 and p = 0.011; respectively). Furthermore, these patients with high level of TGF-βR1 expression had a significantly better prognosis than those with low TGF-βR1 expression in the tumor (p = 0.021). Luminal B HER2 negative tumors with TGF-βRI-positive expression tended to be closely associated with the homogeneous ERα expression, although this difference was not significant (p = 0.18). The expression of TGF-βRI was significantly correlated with progression-free survival in luminal B HER2-negative patients (log-rank p = 0.010).
The findings of the present study suggest that TGF-βRI may be used as a potential target for the tamoxifen treatment of luminal B breast cancer patients with HER2-negative phenotype. Further study is required to assess the possible relationship between the TGF-β family proteins and tamoxifen responsiveness in luminal HER2 positive breast cancer.
Legal entity responsible for the study
Russian Scientific Foundation, grant #19-75-30016.
All authors have declared no conflicts of interest.