T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study

Abstract

BackgroundThe issue of a potential association between thyroid conditions/hormones and breast cancer has been studied extensively during the last decades but the results have been inconclusive and almost no studies have investigated breast cancer aggressiveness. We have previously found a positive association between prospectively measured levels of triiodothyronine (T3) and breast cancer incidence as well as breast cancer mortality. We now investigated prediagnostic T3 levels in relation to specific prognostic factors in breast cancer.MethodsThe Malmö Preventive Project is a population-based prospective cohort including 2185 women in whom T3 levels were measured at baseline. That is, total T3 levels were measured before a potential diagnosis of breast cancer. Mean follow-up was 23.3 years and 149 women in the study population were diagnosed with invasive breast cancer. Tumours were classified according to selected prognostic factors of breast cancer; i.e. grade, tumour size, lymph node metastasis, and hormonal receptor status. T3 was handled both as tertiles and as a continuous variable. A Cox’s proportional hazards analysis yielded hazard ratios with 95% confidence intervals. All analyses were also restricted to postmenopausal women.ResultsOverall there was a statistically significant association between T3 and “all” breast cancers. The adjusted Hazard Ratio (HR) in the third tertile, as compared to the first, was (1.61:1.07-2.43). There was a statistically significant positive association between the third T3 tertile and large tumours, i.e. > 20 mm, (3.17:1.20-8.36) and the occurrence of lymph node metastases, (4.53:1.60-12.83). Other prognostic factors positively associated with T3 were negative oestrogen receptor (ER) status, (3.52:1.32-9.41) and negative progesterone receptor (PGR) status, (3.52:1.42-8.75). The analyses of T3 as a continuous variable and analysis restricted to postmenopausal women, confirmed the results but also showed an association with smaller tumours and in postmenopausal women a contemporary association with negative lymph nodes.ConclusionsThis prospective study of serum T3 levels in relation to breast cancer aggressiveness is the first of its kind. We found statistically significant positive associations between higher prediagnostic T3 levels and larger tumours, occurrence of lymph node metastases, and negative ER and PGR status.

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 . 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 . However, the association with breast cancer was of borderline statistical significance in the overall group and the association was not related to the number of liothyronine prescriptions, which raises doubt as to whether this association is causally related or not.…”

Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative

“…Evidence from epidemiological studies on postmenopausal women suggests that an increased T3/E2 ratio may promote breast cancer development (14,34,35). T3 levels have also been shown to have a positive correlation with breast cancer tumor size and the risk of lymph node metastasis in populationbased studies (36).…”

Thyroid disorders and breast cancer risk in Asian population: a nationwide population-based case–control study in Taiwan

“… 13 In population-based studies, T3 levels have also been found to have a positive correlation with breast cancer tumour size and the risk of lymph node metastasis. 31 …”