Thyroid disease and breast cancer risk in the Sister Study

Background: Thyroid disease (TD), and its treatments, are suspected risk factors for breast cancer (BC), 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 BC in a large cohort of US women. Methods: Data are from the Sister Study, a prospective cohort of 50,884 US women with no BC 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 BC. Results: Of 45,783 eligible participants, 11,567 reported TD at baseline and over follow-up (hyperthyroidism: n=1,710; hypothyroidism: n=9,857) and 3,897 participants subsequently developed BC. Breast cancer HR was 1.15 (CI:0.95, 1.39) for those with hyperthyroidism and 0.93 (CI:0.85, 1.01) for those with hypothyroidism, compared to no thyroid disease, with similar patterns observed across racial and ethnic groups. Hyperthyroidism was associated with greater premenopausal BC hazard (HR=1.85, CI:1.11, 3.07) and differed from BC hazard for hypothyroidism, which appeared reduced (HR=0.75, CI:0.54, 1.05) but did not reach statistical significance (p-heterogeneity=0.06). BC 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 elevated BC risk, particularly premenopausal BC. Impact: Although more research is needed, premenopausal women treated for hyperthyroidism may benefit from enhanced breast cancer screening.