The TSH/Thyroid Hormones Axis and Breast Cancer

Breast cancer, the most prevalent female carcinoma, is characterized by the expression of steroid nuclear receptors in a subset of cases. The most important nuclear receptor with prognostic and therapeutic implications is the Estrogen Receptor (ER), which is expressed in about three out of four breast cancers. The Progesterone Receptor (PR) and the Androgen Receptor (AR) are also commonly expressed. Moreover, non-steroid nuclear receptors, including the vitamin D receptor (VDR) and the thyroid receptors (TRs), are also present in breast cancers and have pathophysiologic implications. Circulating thyroid hormones may influence breast cancer risk and breast cancer cell survival, through ligating their canonical receptors TRα and TRβ but also through additional membrane receptors that are expressed in breast cancer. The expression of TR subtypes and their respective isotypes have diverse effects in breast cancers through co-operation with ER and influence on other cancer-associated pathways. Other components of the TSH/thyroid hormone axis, such as TSH and selenoiodinase enzymes, have putative effects in breast cancer pathophysiology. This paper reviews the pathophysiologic and prognostic implications of the thyroid axis in breast cancer and provides a brief therapeutic perspective.