Thyroid hormones and breast cancer association according to menopausal status and body mass index

Abstract

BackgroundThyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women.MethodsTo assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models.ResultsHigher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01–11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17–3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed.ConclusionsThere is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1017-8) contains supplementary material, which is available to authorized users.

Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study

“…We found that the association between thyroid function and incident breast cancer did not significantly differ by obesity among premenopausal and postmenopausal women. It is difficult to directly compare our findings with previous studies because we used FT4 serum concentration while previous studies used TT4 . Only a previous study by Ortega‐Olvera et al evaluated the effect modification by obesity in premenopausal and postmenopausal women and demonstrated that effect of TT4 on breast cancer increased as BMI increased in postmenopausal women .…”

“…31 Only a previous study by Ortega-Olvera et al evaluated the effect modification by obesity in premenopausal and postmenopausal women and demonstrated that effect of TT4 on breast cancer increased as BMI increased in postmenopausal women. 31 This finding is in line with our finding but in the present study, we could not reach significant conclusion due to insufficient outcome events despite relatively large sample size. Several mechanisms have been hypothesized to explain the association between thyroid hormones and breast carcinogenesis.…”

“…31 Only a previous study by Ortega-Olvera et al evaluated effect modification by obesity in premenopausal and postmenopausal women and demonstrated that the effect of TT4 on breast cancer increased as BMI increased in postmenopausal women. 31 This finding is in line with our findings, but in the present study the number of outcome events may have been insufficient to reach statistical significance despite a relatively large sample size. Future research is needed to elucidate the role of thyroid function in breast cancer risk according to tumor pathology such as TNM stage at diagnosis, grade of tumor, and estrogen receptor, progesterone receptor and HER-2 status while considering possible modification by postmenopausal status and obesity.…”

Exogenous Thyroid Hormone Is Associated with Shortened Survival and Upregulation of High-Risk Gene Expression Profiles in Steroid Receptor–Positive Breast Cancers

“…Even in cases of benign thyroid disease, elevated serum thyroid-stimulating hormone (TSH) or triiodothyronine (T3) independently or in combination with estrogen, have been associated with a higher rate of BC and more rapid cancer progression in some studies (4)(5)(6). A meta-analysis of multi-national trials have demonstrated that BC is the most common secondary malignancy in female patients with thyroid cancer (6,7), and BC patients have a significantly higher risk of thyroid cancer; thus the relationship appears to be hormonal in nature and bidirectional (7)(8)(9). Preclinical models and in Research.…”

Tetrac as an anti-angiogenic agent in cancer

“…In this context, again both hyperthyroidism and hypothyroidism have been shown to influence cancer onset in both directions and thus no clear consensus exists. As this goes beyond the scope of the current review, please refer to recent studies and reviews for more information on the subject (Hellevik et al 2009, Khan et al 2016, Chan et al 2017, Ortega-Olvera et al 2018reviewed in Hercbergs et al 2010, Moeller & Führer 2013.…”