Thyroid hormone receptor α in breast cancer: prognostic and therapeutic implications

We determined the expression of two transcriptional variants of thyroid hormone receptor alpha (THR alpha 1 and THR alpha 2) in samples from a cohort of breast cancer patients and correlated expression levels with survival. 130 women who were diagnosed with invasive breast carcinoma between 2007 and 2008 were included. Representative sections of their tumours were analyzed in triplicate on a tissue microarray for expression of THR alpha 1 and THR alpha 2 by immunohistochemistry. The prognostic significance of THR alpha 1 and THR alpha 2 expression was assessed using Kaplan-Meier survival analyses, adjusted for known prognostic factors. Seventy-four percent of tumours had high expression of THR alpha 1 (Allred score a parts per thousand yen6) and 40 % had high expression of THR alpha 2. Expression of THR alpha 2 correlated positively with ER expression (p < 0.001) and with PR expression (p < 0.001), but negatively with HER2 expression (p = 0.018). Patients with low THR alpha 2 expression had inferior 5-year overall survival (75.3 %) compared to those with high expression (91.7 %; p = 0.06). In a multivariate model, high THR alpha 2 expression was a significant and independent prognosticator of improved overall survival (HR = 0.84; 95 % CI 0.71-0.98). Many breast tumours express THR alpha 2 at high levels and these patients experience improved survival. Thyroid hormone signalling may be important in a proportion of breast cancers and THR alpha 2 expression may be a regulator of signalling in this pathway.