Thyroid hormone receptors in breast cancer: prognosis, predictive and therapeutic implications.
Researchers: Dr. B Dhesy
The survival of breast cancer patients has improved in the past 20 years due to advancements in systemic therapy e.g. endocrine therapy, chemotherapy, and anti-HER2 directed therapy. These therapies benefit patients whose cancers display hormone receptors called estrogen receptor (ER) and/or progesterone receptor (PR), or a cancer promoting protein called HER2. However, not all breast cancer tumours with hormone receptors respond well to endocrine therapy and tumours that are ER, PR, and HER2 negative are associated with a poor outcome. Thyroid hormones can influence key cellular functions including proliferation and metabolism. Thyroid hormones act through thyroid hormone receptors (THRs). We hypothesized that expression of THRs would correlate with hormone receptors and correlate with outcomes.
Stored tissue samples from a cohort 130 women who were diagnosed with invasive breast carcinoma between 2007 and 2008 were retrieved. The expression of two transcriptional variants of thyroid hormone receptor alpha (THRα1 and THRα2) was measured. The expression levels were correlated with survival. Patients with low THRα2 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 THRα2 expression was a significant and independent prognosticator of improved overall survival (HR = 0.84; 95 % CI 0.71-0.98). The conclusion of this study was that many breast tumours express THRα2 at high levels and these patients experience improved survival. This is an interesting observation that needs validation in a larger study. It may explain why some tumors that are hormone receptor positive may still not respond well to endocrine therapy.