Thyroid function and survival outcomes in women with uterine cancer

Abstract

Objectives: Loss of estrogen and progesterone receptor expression has historically been associated with poor survival outcomes in women with uterine cancer, but the role of the remaining 46 nuclear hormone receptors remains unclear. Recently, data from The Cancer Genome Atlas demonstrated a novel association between loss of thyroid hormone receptor beta expression and increased survival in uterine cancer patients.1 The purpose of this study was to explore the association between clinical indices of thyroid function and survival outcomes in women diagnosed with uterine cancer. 1. Pique, D.G., Greally, J.M. & Mar, J.C. Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival. BMC Cancer 20:857 (2020). Methods: A single-institution retrospective cohort study was performed examining all women diagnosed with uterine cancer from 2006-2016. Data regarding patient demographics, medical co-morbidities, histology, stage and treatment course were abstracted from the medical record. Historical records and thyroid function studies (TSH, T3, free T4) were used to identify patients who were euthyroid, hypothyroid, or hyperthyroid within 1 year prior to their cancer diagnosis until the end of the follow-up period. The primary outcome was time to death from cancer diagnosis. A Cox proportional hazards model was used to identify the association between thyroid dysfunction and survival by using thyroid status as a time-dependent covariate and adjusting for age, grade and stage of disease. Download : Download high-res image (177KB) Download : Download full-size image Results: A total of 1201 patients were included for analysis. One thousand thirty (86%) patients had no thyroid dysfunction at time of cancer diagnosis, 145 patients (12%) carried the baseline diagnosis of hypothyroidism and 26 patients (2%) had hyperthyroidism. Twenty three women with normal thyroid function at baseline developed thyroid dysfunction during follow-up (91% hypothyroid, 9% hyperthyroid). A total of 218 deaths were observed. There were no differences in survival among patients with hypothyroidism or hyperthyroidism compared to euthyroid patients [HR 0.72 (95% CI 0.47-1.12, p=0.15); HR 0.51 (95% CI 0.16-1.58, p=0.24) respectively]. Women diagnosed with thyroid dysfunction prior to cancer diagnosis were observed to have a 30% lower hazard of death compared to euthyroid women, although this did not achieve statistical significance [HR 0.70 (95% CI 0.46-1.07, p=0.10)]. Patients who developed thyroid dysfunction after cancer diagnosis were observed to have a 3.7 fold higher hazard of death compared to patients who remained euthyroid during followup [HR 3.70 (95% CI 1.60-8.30), p=0.01], but this did not maintain significance in models adjusting for age, grade and stage of disease. Conclusions: Thyroid dysfunction was not associated with a difference in survival in women with uterine cancer in our cohort. Timing of thyroid dysfunction relative to uterine cancer diagnosis may affect clinical outcomes. Additional studies are needed to explore the relationship of thyroid dysfunction and uterine cancer.