Association Between Thyroid Dysfunction and Breast Cancer Risk Among Adult Women ; Association entre dysfonction thyroïdienne et risque de cancer du sein chez la femme adulte

Long-term outcomes of thyroid dysfunction (hyper- and hypothyroidism) among adult women remain unclear, with continuing debates on the effect of abnormal thyroid hormone levels and thyroid dysfunction treatments (e.g radioactive iodine - RAI) on cancer risk. This thesis project aimed to evaluate the association between the risk of female breast cancer and thyroid dysfunction, while accounting for thyroid dysfunction treatments, comorbidities, and breast cancer risk factors. The project was mainly based on the UK Biobank (UKB) cohort, which included 273,375 women aged 40-69 years at inclusion between 2006 and 2010. Detailed data on personal and family medical history, medications, lifestyle, reproductive and socioeconomic characteristics were collected. The UKB cohort has been linked to regional and national hospital inpatient databases, cancer and death registries (5,326 incident breast cancer cases reported during a median followup time of 7 years). We found no significant association between breast cancer risk and either overall hyper- or hypothyroidism. However, breast cancer risk was ~40% higher among women treated for hyperthyroidism compared to women with no thyroid dysfunction, regardless of the treatment modality. No increased risk was observed among untreated women, suggesting an effect hyperthyroidism severity and/or etiology. When combining those results with all evidence currently available in the litterarure, we estimated a pooled risk ratio of 1.15 and 0.86 for hyper- and hypothyroidism (treated or not), respectively, compared to no thyroid dysfunction. In the meta-analysis, breast cancer risk was significantly lower among premenopausal women with hypothyroidism, and increased, although insignificantly, among postmenopaused women with hyperthyroidism. The analyses were extended to a European pooled cohort of 8,475 female thyroid cancer survivors (335 breast cancer cases reported during a median follow-up time of 12.7 years), to investigate the role of RAI in breast cancer incidence. We found a ...