Background Circulating sex hormones and growth factors have been associated with the risk of invasive breast cancer, but the nature of these relationships is not fully understood. We used data from UK Biobank, a large study with hormone measures on the full cohort and repeat measures in a sub-sample, to estimate the magnitudes of the associations after allowing for measurement error.

Methods We included 30,565 pre-menopausal and 133,294 post-menopausal women in this analysis. Hormone concentrations were measured in serum collected between 2006 and 2010, and incident cancer cases were identified through linkage to national cancer and death registries. Multivariable Cox proportional hazards models were used, and hazard ratios (HRs) were corrected for regression dilution using repeat measures collected in about 5,000 women four years after recruitment (except for oestradiol).

Results During a median follow-up of 7.1 years, 527 pre-menopausal and 2,997 post-menopausal women were diagnosed with invasive breast cancer. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in premenopausal women (p_{heterogeneity}=0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); p_{heterogeneity}=0.2), and inversely associated with SHBG (sex hormone binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); p_{heterogeneity}=0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone.

Conclusion This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.