Thyroid Disease and Breast Cancer Risk in the Sister Study.

Abstract

Background: Thyroid disease and its treatments are suspected risk factors for breast cancer, attributed primarily to alterations in thyroid hormone-related metabolism. Prior literature is inconsistent, in part, due to small sample sizes. We, therefore, assessed the effects of hyper- and hypothyroidism on incident breast cancer in a large cohort of US women.

Methods: Data are from the Sister Study, a prospective cohort of 50,884 US women with no breast cancer history at enrollment (2003-2009; ages 35-74 years) and follow-up through September 2021. We used time-varying Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between self-reported thyroid diseases and treatments and incident breast cancer.

Results: Of 45,783 eligible participants, 11,567 reported thyroid disease at baseline and over follow-up (hyperthyroidism: n = 1,710; hypothyroidism: n = 9,857), and 3,897 participants subsequently developed breast cancer. Breast cancer HR was 1.15 (95% CI, 0.95-1.39) for those with hyperthyroidism and 0.93 (95% CI, 0.85-1.01) for those with hypothyroidism, compared with no thyroid disease, with similar patterns observed across racial and ethnic groups. Hyperthyroidism was associated with greater premenopausal breast cancer hazard (HR = 1.85; 95% CI, 1.11-3.07) and differed from breast cancer hazard for hypothyroidism, which seemed reduced (HR = 0.75; 95% CI, 0.54-1.05) but did not reach statistical significance (Pheterogeneity = 0.06). Breast cancer hazards were higher, albeit not statistically significant, for those treated for hyperthyroidism but not hypothyroidism.

Conclusions: Women diagnosed with hyperthyroidism or receiving related treatment may have an elevated breast cancer risk, particularly for premenopausal breast cancer.

Impact: Although more research is needed, premenopausal women treated for hyperthyroidism may benefit from enhanced breast cancer screening.