Thyroid-stimulating hormone and thyroid hormones in women with breast cancer: effects of neoadjuvant chemotherapy and menopausal status
image: The effects of neoadjuvant chemotherapy in postmenopausal women on TSH and fT4, when compared with untreated postmenopausal women with breast cancer, are summarized in (c). Panel A highlights that both untreated breast cancer patients and those undergoing NCh exhibit an increase in TSH and fT4 levels compared to healthy premenopausal controls. Notably, premenopausal women receiving NCh display a more pronounced elevation in TSH, suggesting a potential impact of the tumor itself and the chemotherapy treatment on thyroid hormone regulation in this group. Panel B focuses on postmenopausal women, demonstrating that, similar to their premenopausal counterparts, both untreated and NCh-treated breast cancer patients show elevated TSH and fT4 levels compared to control postmenopausal women. However, in contrast to premenopausal women, postmenopausal women treated with NCh exhibit a smaller increase in fT4 compared to untreated postmenopausal breast cancer patients, indicating a difference in the effect of NCh on thyroid hormones based on menopausal status. Finally, the data in panel C underscore that postmenopausal women with breast cancer who received NCh showed a significantly reduced increase in fT4 compared to untreated postmenopausal women with breast cancer. These findings suggest that while breast cancer generally leads to elevated levels of TSH and fT4, neoadjuvant chemotherapy has a distinct modulating effect on fT4 levels, further demonstrating a complex interplay between menopausal status, breast cancer, and thyroid hormone levels. The importance of monitoring thyroid function in breast cancer patients, considering their menopausal status and chemotherapy treatment, in relation to the complex interplay between tumor progression and the effectiveness of oncologic treatment, is emphasized. fT3, free triiodothyronine; rT3, reverse triiodothyronine; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone.
Credit: José Manuel Martínez-Martos
Background and objectives
The development and progression of breast cancer may be influenced by thyroid hormone levels. In this study, we investigated thyroid function in pre- and postmenopausal women with breast cancer, with and without neoadjuvant chemotherapy (NCh).
Methods
The study included 198 women diagnosed with infiltrating ductal carcinoma: 83 did not receive NCh (39 premenopausal and 44 postmenopausal), while 115 underwent NCh before surgery (63 premenopausal and 52 postmenopausal). Additionally, 78 healthy volunteers, aged 28 to 69 years, served as the control group. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were quantified using chemiluminescent immunoassays.
Results
We observed a significant increase in serum TSH and fT4 levels in both pre- and postmenopausal women with breast cancer, regardless of NCh treatment, compared to control subjects. However, postmenopausal women with breast cancer who received NCh showed lower fT4 levels than their untreated counterparts. Notably, fT3 levels increased only in premenopausal women with breast cancer who underwent NCh, compared to both the premenopausal control group and untreated premenopausal breast cancer patients.
Limitations and Conclusions
While our results indicate a significant alteration in thyroid function in women with breast cancer, irrespective of their menopausal status and NCh treatment, the study is constrained by several limitations. Firstly, the lack of longitudinal data. Our cross-sectional design limits causal inferences and cannot clarify whether thyroid hormone alterations precede breast cancer or result from tumor progression or therapy. Secondly, our study does not account for anti-thyroid antibodies or iodine status, which are important factors in considering autoimmune thyroid diseases (e.g., Hashimoto’s thyroiditis) that are common in women and could confound hormone measurements. Thirdly, our cohort exclusively includes patients with infiltrating ductal carcinoma, limiting generalizability to other breast cancer subtypes. Finally, we present a relatively modest sample size, which restricts the generalizability of our conclusions to larger populations and diverse clinical settings. Furthermore, although we have meticulously controlled for several variables, such as smoking, alcohol consumption, and chronic conditions, we recognize that other factors not assessed in this investigation may also influence thyroid hormone levels and their interaction with breast cancer. In fact, the limitations in sample size did not yield statistically significant differences in the studied cohort when stratified by molecular subtype, Scarff-Bloom-Richardson grading, and pathological classification. Future research with larger cohorts and more diverse populations, as well as the incorporation of additional clinical and molecular data, is necessary to corroborate our results and to further elucidate the complex interplay between thyroid hormones and breast cancer. Specifically, the potential impact of other medications, environmental factors, and lifestyle choices on thyroid function in breast cancer patients should be considered. The assessment of long-term effects of chemotherapy on thyroid function also remains an important area for future research. A recent hypothesis-generating review emphasizes the need to explore thyroid hormone receptor isoforms as prognostic biomarkers, aligning with our call for molecular profiling.
We conclude that the observed alterations in thyroid function, specifically the increase in serum TSH and fT4 levels, suggest a potential role for thyroid hormones in breast cancer progression, thereby highlighting the need for closer monitoring of thyroid function in breast cancer patients. This observation takes on special relevance in light of the demonstrated influence of thyroid hormones on tumor proliferation and the effectiveness of chemotherapy treatment. However, these findings cannot be interpreted as definitive conclusions regarding the specific mechanisms driving the observed effects, nor do they imply a direct causal relationship between thyroid function and breast cancer outcomes. Future studies should focus on the clinical utility of thyroid hormone monitoring and potential interventions that could improve outcomes for these patients.
Full text
https://www.xiahepublishing.com/2996-3427/OnA-2024-00033
The study was recently published in the Oncology Advances.
Oncology Advances is dedicated to improving the diagnosis and treatment of human malignancies, advancing the understanding of molecular mechanisms underlying oncogenesis, and promoting translation from bench to bedside of oncological sciences. The aim of Oncology Advances is to publish peer-reviewed, high-quality articles in all aspects of translational and clinical studies on human cancers, as well as cutting-edge preclinical and clinical research of novel cancer therapies.
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