It is well established that cyclin D1 is an important component of estrogen regulation. We have previously reported that the transforming growth factor beta type I receptor (TβRI) is related to tamoxifen-sensitive tumors. In addition to TβRI, the type 2 receptor (TβRII) plays a key role in the regulation of TGF-β signaling.The aim of the present study was to explore the predictive value of cyclin D1/TβRII expression for the tamoxifen response in patients with hormone receptor-positive breast cancer.
Expression of cyclin D1 and TβRII by flow cytometry and their mRNA expression by quantitative real-time polymerase chain reaction was performed on tissue specimens from 60 women with hormone receptor-positive primary breast cancer who had received adjuvant tamoxifen treatment at a dose of 20 mg/day for at least 5 years. The primary end-point was progression-free survival (PFS).
High mRNA expression of TβRII in tumor were significantly related to tamoxifen efficacy (р = 0.026). Co-expression analysis revealed that the population of cyclin D1-/TβRII+ was more prevalent in the tamoxifen-sensitive tumors (p=0.009). We showed a significant correlation between the TβRII and cyclin D1 expression (r = 0.39; p = 0.010). Low cyclin D1 expression as well as TβRII high expression tended to be closely associated with a better prognosis, although this difference was not significant (log-rank p = 0.08 and log-rank p = 0.09, respectively).
The findings of the present study indicate that cyclin D1-/TβRII+ cells may be involved in the tamoxifen response and are associated with sensitivity to this drug.
The authors.
The study was supported by the Russian Scientific Foundation, grant #19-75-30016.
All authors have declared no conflicts of interest.