Abstract C184: Thyroid hormone receptors: Future targets for breast cancer therapy?.
Authors: Jerzak Katarzyna J. , Bane Anita , Dhesy-Thind Bindi 
Published: August 2014

Introduction: Thyroid receptors (TR) have been documented in breast cancer tissue. Given their role in cell metabolism and proliferation, they may serve as future therapeutic targets. Prior to targeting TRs for therapy, their prevalence and degree of expression must be elucidated. In this study, the expression and sub-cellular location of three TR isoforms (TRA1, TRA2, TRB1) in breast cancer tissue is documented and correlated to standard pathological and clinical prognostic markers.

Methods: 131 archived breast tumors were selected sequentially starting from January 2007, to allow for collection of 5-year overall survival (OS) and disease-free survival (DFS) data. The tumors were assessed retrospectively for TRA1, TRA2 and TRB1 expression by immunohistochemistry, using commercially available antibodies. Nuclear versus cytoplasmic location was noted. The Allred score of each tumor was assessed in triplicate; an average score ≥5 was considered significant in the statistical analysis. TR expression was correlated with pathological markers (ER/PR and Her2/neu positivity, tumor size, grade, nodal involvement, lymphovascular invasion, mitotic count) and clinical factors (age, OS, DFS) using correlation analyses and binary regression models.

Results: The age of patients was 65±15 (mean± standard deviation) years. The majority had T1c (31%) or T2 (56%) disease, and 39% had lymph node involvement. 60% of tumors were ER positive and 13% were Her2/neu positive. TRs were expressed to some extent in 130 of 131 assessed breast tumors; TRA1 was highly expressed (Allred score ≥5) in 81% of tumors, while TRA2 and TRB1 were highly expressed in 51% and 29% of tumors, respectively. TRA1 and TRA2 were expressed in the nucleus, while 95% of TRB1 receptors were expressed in the cytoplasm. Cytoplasmic TRB1 expression was associated with a mitotic count &lt;10 [OR 0.4 (95%CI 0.20-0.93), p=0.03], but not with other variables. High TRA2 expression was associated with ER [OR 5.5 (95%CI 2.2-13.7), p&lt;0.01] and PR [OR 5.3 (95%CI 2.4-11.8), p&lt;0.01] positivity, and also 5-year DFS [OR 2.6 (95%CI 1.1-6.1), p=0.03]. Conversely, low TRA expression was associated with Her2/neu positivity [OR 3.2, (95%CI 1.0-9.5), p=0.04], high tumor grade [OR 6.0, (95%CI 2.3-15.2), p&lt;0.01] and a mitotic count &gt;10 [OR 2.8, (95%CI 1.4-5.8), p=0.05]. There was no significant association between TR expression and tumor size, lymph node involvement or OS.

Conclusion: Thyroid receptors are widely expressed in breast cancer and they are known to influence cellular proliferation. High TRA2 expression is statistically significant in predicting favorable pathologic markers and even 5-year DFS. As with ER, its favorable prognostic profile should not exclude TRA2 as a therapeutic target; it may have the potential to expand our armamentarium of hormone directed therapies.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C184.

Citation Format: Katarzyna J. Jerzak, Anita Bane, Bindi Dhesy-Thind. Thyroid hormone receptors: Future targets for breast cancer therapy?. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C184.