Since BRCA1 associated breast
cancers are frequently classified as
hormone receptor negative or even triple negative, the application of endocrine
therapies is rather limited in these patients. Like
hormone receptors that bind to
estrogen or
progesterone,
thyroid hormone receptors (TRs) are members of the
nuclear hormone receptor superfamily. TRs might be interesting
biomarkers - especially in the absence of classical
hormone receptors. The current study aimed to investigate whether TRs may be specifically expressed in BRCA1 associated
cancer cases and whether they are of prognostic significance in these patients as compared to sporadic
breast cancer cases. This study analyzed TRα and TRβ immunopositivity in BRCA1 associated (n = 38) and sporadic
breast cancer (n = 86). Further, TRs were studied in MCF7 (BRCA1 wildtype) and HCC3153 (BRCA1 mutated) cells. TRβ positivity rate was significantly higher in BRCA1 associated as compared to sporadic breast
cancers (p = 0.001). The latter observation remained to be significant when cases that had been matched for clinicopathological criteria were compared (p = 0.037). Regarding BRCA1 associated
breast cancer cases TRβ positivity turned out to be a positive prognostic factor for five-year (p = 0.007) and overall survival (p = 0.026) while TRα positivity predicted reduced five-year survival (p = 0.030). Activation of TRβ resulted in down-modulation of CTNNB1 while TRα inhibition reduced cell viability in HCC3153. However, only BRCA1 wildtype MCF7 cells were capable of rapidly degrading TRα1 in response to T3 stimulation. Significantly, this study identified TRβ to be up-regulated in BRCA1 associated
breast cancer and revealed TRs to be associated with patients' prognosis. TRs were also found to be expressed in triple negative BRCA1 associated
breast cancer. Further studies need to be done in order to evaluate whether TRs may become interesting targets of endocrine therapeutic approaches, especially when
tumors are triple-negative.