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Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

Sandar Tin Tin 1Gillian K Reeves 2Timothy J Key 2

Br J Cancer. 2021 Apr 16. doi: 10.1038/s41416-021-01392-z. 


Background: Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood.

Methods: UK Biobank was used. Hormone concentrations were measured in serum collected in 2006-2010, and in a repeat subsample (N ~ 5000) in 2012-13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias.

Results: Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. 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 pre-menopausal women (pheterogeneity = 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); pheterogeneity = 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); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone.

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