We investigated thyroid hormone levels in menopausal BrC patients and verified the action of triiodothyronine on genes regulated by estrogen and by triiodothyronine itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum TPO-AB, TSH, FT4, and estradiol, before and after surgery, and used immunohistochemistry to examine estrogen and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, triiodothyronine, triiodothyronine plus 4-hydroxytamoxifen, 4-hydroxytamoxifen, estrogen, or estrogen plus 4-hydroxytamoxifen. Genes regulated by estrogen (TGFA, TGFB1, and PGR) and by triiodothyronine (TNFRSF9, BMP-6, and THRA) in vitro were evaluated. TSH levels in BrC patients did not differ from those of the control group (1.34 ± 0.60 versus 2.41 ± 1.10？μU/mL), but FT4 levels of BrC patients were statistically higher than controls (1.78 ± 0.20 versus 0.95 ± 0.16？ng/dL). TGFA was upregulated and downregulated after estrogen and triiodothyronine treatment, respectively. Triiodothyronine increased PGR expression; however 4-hydroxytamoxifen did not block triiodothyronine action on PGR expression. 4-Hydroxytamoxifen, alone or associated with triiodothyronine, modulated gene expression of TNFRSF9, BMP-6, and THRA, similar to triiodothyronine treatment. Thus, our work highlights the importance of thyroid hormone status evaluation and its ability to interfere with estrogen target gene expression in BrC samples in menopausal women. 1. Introduction For many years, associations between thyroid disorders and breast cancer (BrC) have raised questions regarding the involvement of thyroid hormone (TH) (either associated with estrogen receptor or not) on the development and progression of breast cancer, and significant research efforts have focused on this area [1–10]. Recently a study first showed that TH levels in postmenopausal women are positively related to BrC risk in a dose-response manner [9]. Prognostic and predictive factors are indispensable tools in neoplastic disease treatment [11], and estrogen receptor (ER) concentration is an important parameter in BrC prognosis [12]; ER status is an important consideration for BrC antiestrogen treatment [13]. Therefore, the presence and concentration of ER provide crucial information regarding tumors that respond to hormonal intervention [14]. Positive ER detection in BrC tissues is an indication of a tumor with hormonal dependence and indicates the benefit of endocrine therapy to this type of BrC [15].
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