ROLE OF TRANSFORMING GROWTH FACTOR RECEPTOR B I TYPE (TGF-BRI) IN THE PROGRESSION OF THE LUMINAL BREAST CANCER SUBTYPE

Introduction. The crosstalk between the estrogen and growth factor receptors signaling may play an important role in the resistance to endocrine therapy. The aim of the study was to examine the relationship between the protein and receptor gene expression of transforming growth factor β type I (TGF-βRI) and its polymorphism with progression of luminal breast cancer patients treated by adjuvant tamoxifen.

Material and methods.  The study included 105 patients with luminal breast cancer (T_1-3N_0–3M₀), who had received adjuvant tamoxifen  at a dose of 20 mg/day for at least 5 years. Patients who developed distant metastasis or recurrence after tamoxifen therapy were defined as tamoxifen resistance (TR) group, while distant metastasis-free patients were analyzed as tamoxifen sensitive (TS) group. TGF-βRI expression level was evaluated using immunohistochemistry. TGF-BRI gene expression and genotypes for rs334354 SNP were detected by a Real-time PCR.

Results. We found high TGF-βRI gene expression in patients with luminal A subtype compared with luminal B breast cancer (p=0.050). The Int7G24AA and Int7G24A mutant carriers were more prevalent in luminal A breast cancer patients (p=0.019 and p=0.007, respectively). TGF-βRI protein expression level was significantly higher in the tamoxifen sensitive group compared to tamoxifen resistance breast cancer patients regardless of molecular subtypes (p=0.043). There was a trend for a tamoxifen sensitivity among luminal B breast cancer patients with a high TGF-βRI protein expression (p=0.090).

Conclusion. TGF-βRI protein expression level can be a potential molecular marker of tamoxifen resistance in luminal breast cancer patients.

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