Triiodothyronine and breast cancer

Abstract

The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Thyroid hormone; Triiodothyronine; Breast cancer; Mammary gland and metabolism Core tip: Breast cancer (BC) is a malignant tumor occurring much more frequently in women than in men; worldwide, the incidence of BC has increased markedly in recent years. It is estimated that 1.7 million women will be diagnosed with BC in 2020, marking an increase of 26%, compared to the current incidence: 1.35 million new cases annually. Countless environmental risk factors, pathological conditions, and physiological agents, as well as thyroid hormones (THs), have been involved in the development of BC. Various lines of evidence suggest tumor-promoting effects of THs. The literature contains controversial reports regarding the relationship between thyroid diseases and BC; furthermore, studies reporting both an excess of and a lack of THs may affect breast development and progression to cancer. Epidemiologically, many studies suggest that hyperthyroidism is a factor in the development of BC. Furthermore, experimental studies have shown that high levels of THs reduce the interval of multiplication of BC cell lines. Therefore, the influence of THs on BC is unclear. However, the majority of BC research suggests a relationship, primarily, when the molecular aspects of these hormones are considered in the progression of this type of tumor.De Sibio MT, de Oliveira M, Moretto FCF, Olimpio RMC, Conde SJ, Luvizon AC, Nogueira CR. Triiodothyronine and breast TOPIC HIGHLIGHT Triiodothyronine and breast cancer INTRODUCTIONThyroid hormones (THs), 3,5,3′,-triiodothyronine (T3) and thyroxine (T4), play critical roles in the differentiation, growth, metabolism, and physiological function of nearly all mammalian tissues [1,2] ; in addition, they are required for amphibian metamorphosis [3] ....

Current concepts and challenges to unravel the role of iodothyronine deiodinases in human neoplasias

“…3A and C). As THs influence the proliferation of breast cancer cells, it is worthwhile to consider that DIO3 expression in mammary neoplasias may play a role in modulating intracellular T 3 levels and thus contribute to tumor progression (De Sibio et al 2014). We observed moderate immunostaining of DIO3 in normal human mammary gland tissue and a significant expression of DIO3 staining in samples of invasive ductal carcinoma (I M Goemann, V Marczk, A L Maia, unpublished observations).…”

Liothyronine use in a 17 year observational population‐based study ‐ the tears study

“…In breast cancer cell lines it has been demonstrated that tri-iodothyronine can augment the cell proliferation potential of estrogens, thus possibly increasing the malignant potential in breast cancer cells lines. 31,32 This is supported by a recent trial where higher endogenous serum tri-iodothyronine was associated with breast tumours demonstrating more aggressive characteristics 33 and increased mortality. 34 However, the association with breast cancer was of borderline statistical significance in the overall group and the association was not related to the number Wald test for significance of the variable taken as a whole, v 2 (4) = 33Á64, P < 0Á001.…”

“…The possible association with breast cancer is a concern. In breast cancer cell lines it has been demonstrated that tri‐iodothyronine can augment the cell proliferation potential of estrogens, thus possibly increasing the malignant potential in breast cancer cells lines . This is supported by a recent trial where higher endogenous serum tri‐iodothyronine was associated with breast tumours demonstrating more aggressive characteristics and increased mortality .…”

Thyroid hormone receptor α in breast cancer: prognostic and therapeutic implications

“…If this is the case, then among the subgroup of breast cancer patients expressing THRa1, it may be hypothesized that outcomes might be improved by (a) lowering the systemic levels of thyroid hormone [26][27][28], (b) inhibiting THRa1, or (c) up-regulating THRa2 [29,30]. The possibility of lowering the systemic levels of thyroid hormone using commercially available drugs is intriguing, but further study of this potential therapy is limited by conflicting results regarding the effect of hypothyroidism in women with breast cancer [26][27][28][31][32][33][34][35][36][37][38]. It is possible that the thyroid receptor expression in a breast tumour affects its response to thyroid hormone and that those expressing an ''unfavourable'' thyroid receptor profile may benefit from a reduction in thyroid hormone levels.…”