(Thyroid) Hormonal Regulation of Breast Cancer Cells

Thyroid hormone as L-thyroxine (T4) acts nongenomically at physiological concentrations at its cancer cell surface receptor on integrin αvβ3 (‘thyrointegrin’) to cause cancer cell proliferation. In the case of estrogen receptor (ERα)-positive breast cancer cells, T4 via the integrin promotes ERα-dependent cancer growth in the absence of estrogen. Thus, tumor growth in the post-menopausal patient with ERα-positive cancer may again be ER-dependent because of T4. Additional mechanisms by which T4 may contribute uniquely to aggressive breast cancer behavior—independently of ER—are stimulation of immune checkpoint inhibitor gene expression and of several anti-apoptosis mechanisms. These observations may call for consideration of elimination of host T4 production in breast cancer patients whose response is suboptimal to standard chemotherapy regimens. Euthyroidism in such a setting may be maintained with exogenous 3,3’,5-triiodo-L-thyronine (T3).