Prediagnosis thyroid biomarkers and breast cancer survival: evidence from a European prospective cohort study

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BACKGROUND: Despite improved treatments and survival, breast cancer (bc) remains a leading cause of cancer mortality in women. Thyroid dysfunction has been linked to bc risk, but its impact on bc survival is less clear. We investigated associations between pre-diagnosis thyroid-related biomarkers and all-cause and bc-specific survival. METHODS: A prospective cohort study including 1,513 women with invasive bc from 7 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted. We measured thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and anti-thyroid peroxidase antibodies (Anti-TPO) in samples collected ∼8 years pre-diagnosis. We evaluated associations between these markers and all-cause and bc-specific mortality using Cox proportional hazards models adjusted for relevant covariates. RESULTS: After mean follow-up postdiagnosis of 7 years, 223 deaths occurred, including 161 from bc. We observed no overall associations between circulating levels of TSH, thyroid hormones, thyroid autoimmunity, and mortality. However, in stratified analyses, TSH was inversely associated with all-cause (HR1-standard deviation (SD)=0.70; 95%CI = 0.52-0.94) and bc-specific-mortality (HR1-SD=0.61(0.44-0.84) in premenopausal women, while fT4 was associated with all-cause mortality in metastatic bc (HR1-SD=1.67(1.20 to 2.32), and with bc-specific mortality among users of menopausal/contraceptive hormones (HR1-SD=2.76(1.47-5.19). Anti-TPO-positivity was inversely associated with all-cause mortality in women with body mass index <25kg/m2 and in women with oestrogen receptor-negative tumours, separately. CONCLUSIONS: Thyroid function before diagnosis does not appear to play a major role in bc survival. Although subgroup-specific associations were identified, these findings should be interpreted with caution due to limited statistical power and warrant confirmation in independent populations.

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