T3 and T4 Therapies Present Similar Risks for Breast Cancer and Cancer Mortality

Computer artwork representing breast cancer, with a malignant tumour (red) in a woman’s breast.
Patients treated with triiodothyronine or l-thyroxine experienced similar rates of cancers, all-cause, or cancer-related mortality.

Patients with hypothyroidism treated with triiodothyronine (T3) or l-thyroxine (T4) had similar rates of cancers, all-cause, or cancer-related mortality, according to the results of a long-term registry-based study published in Thyroid.

Data from official registries maintained by the Swedish National Board of Health and Welfare were used for this analysis. Adults (N=575,461) with at least 3 prescriptions for thyroid hormone replacement therapy who did not have a history of breast cancer prior to their first prescription were included. Information on cancer diagnoses and cause of death were assessed.

Patients were stratified into T4-only (n=573,928) and T3 (n=11,147) groups. Most individuals in the T3 group were treated with T4 prior to T3 (n=9614). Within the full sample, patients in the T3 group were notably younger than those in the T4-only group (45.9±13.3 vs 58.6±18.3). In a subsample of new users of T3 or T4, the average age at baseline differed between groups (T4: 54.4±18.6 years and T3: 44.7±13.2 years).

For the full sample, median follow-up time for the T4 group was 8.0 (interquartile range [IQR], 3.7-11.7) years and 2.9 (IQR, 1.3-6.5) years for T3 users, with a total of 4,302,121 person-years of follow-up.

In a univariate analysis of the full sample, breast cancer incidence for women (hazard ratio [HR], 0.782; 95% CI, 0.643-0.951; P =.014) and any cancer for both genders (HR, 0.644; 95% CI, 0.584-0.710; P =0.000) was lower among patients in the T3 group. All-cause mortality (HR, 0.269; 95% CI, 0.242-0.299; P =0.000), mortality from breast cancer among women (HR, 0.482; 95% CI, 0.273-0.850; P =.012), and mortality from any cancer (HR, 0.352; 95% CI, 0.287-0.433; P =0.000) were also lower.

After adjusting for possible cofactors including history of cancers, sex hormone usage, and T3 or T4 dosing, instances of breast cancer among women (adjusted HR [aHR], 0.929; 95% CI, 0.747-1.154; P =.505), any cancer (aHR, 0.968; 95% CI, 0.870-1.077; P =.552), and mortality from breast cancer among women (aHR, 0.910; 95% CI, 0.500-1.657; P =.759) were no longer significant. Patients on T3 therapy had significantly decreased rates of all-cause mortality (aHR, 0.685; 95% CI, 0.608-0.772; P =0.000) and mortality from any cancer among women (aHR, 0.754; 95% CI, 0.586-0.969; P =.028).

Among patients with severe cancer, no significant difference was observed between T3 or T4 treatment for large extension of the primary tumor (aHR, 0.741; 95% CI, 0.535-1.026; P =.071), degree of regional lymph node involvement (aHR, 0.924; 95% CI, 0.584-1.462; P =.737), or metastasis (aHR, 0.700; 95% CI, 0.433-1.130; P =.144).

Study limitations include the lack of laboratory data and the lack of clinical data including body mass index, smoking status, or cause of hypothyroidism.

These data indicated no significant difference between T4 or T3 users for instance of or mortality from breast cancers. However, a dose-dependent model suggested that dosage may be related to underlying health status and may lead to an increase of all-cause mortality among patients prescribed T4.


Planck T, Hedberg F, Calissendorff J, Nlisson A. Triiodothyronine use in hypothyroidism and its effects on cancer and mortality. Published online October 12, 2020. Thyroid. doi: 10.1089/thy.2020.0388