Risk of breast cancer among women with hypo- and hyperthyroidism: Results from a large nationwide cohort study

Experimental evidence links thyroid hormones to breast cancer cell proliferation, but the association between thyroid disorders and breast cancer remains unclear, with previous research yielding conflicting results. This large cohort study investigated the association between hypo- and hyperthyroidism and breast cancer among all women born in Denmark between January 1, 1960, and December 31, 1997 (n = 1,058,939). Data on hypo- and hyperthyroidism diagnoses, cancer diagnoses, covariates, migration, and vital status were obtained from Danish national registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer overall and for histological subtypes were calculated based on adjusted Cox proportional hazard regression models. A total of 49,015 women developed hypothyroidism, 26,950 developed hyperthyroidism, and 15,703 were diagnosed with breast cancer during a median follow-up of 18.8 years. Hypothyroidism was associated with a decreased rate of breast cancer (HR: 0.85, 95% CI 0.78-0.93), with a possible stronger association among postmenopausal women (HR: 0.78, 95% CI 0.68-0.90). In contrast, hyperthyroidism showed no association with breast cancer (HR: 1.00, 95% CI 0.89-1.11), and menopausal status did not affect this association. All findings were consistent across time since first thyroid disease diagnosis and histological subtypes. In conclusion, our study suggests that hypothyroidism is associated with a reduced risk of breast cancer, potentially most pronounced among postmenopausal women, while no association was observed between hyperthyroidism and breast cancer risk. These findings highlight the need for further research to understand the biological mechanisms linking thyroid dysfunction and breast cancer, especially in the context of menopausal status.