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… Click to show full abstract
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).
               
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