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. 2021 Jul;125(1):126-134.
doi: 10.1038/s41416-021-01392-z. Epub 2021 Apr 16.

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

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

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

Sandar Tin Tin et al. Br J Cancer. 2021 Jul.

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Associations of hormones and SHBG with the risk of invasive breast cancer by age at blood collection in pre-menopausal women.
Hazard ratios stratified for age group, region and deprivation; adjusted for age (underlying time variable), ethnicity, educational level, smoking, alcohol, physical activity, BMI, regular menstrual cycle, parity, age at first birth, time since OCP use, presence of endocrine disorders, family history of breast cancer and other hormones and SHBG; and corrected for regression dilution using repeat measures except for total and calculated free oestradiol.
Fig. 2
Fig. 2. Associations of hormones and SHBG with the risk of invasive breast cancer by age at breast cancer diagnosis in pre-menopausal women.
Hazard ratios stratified for age group, region and deprivation; adjusted for age (underlying time variable), ethnicity, educational level, smoking, alcohol, physical activity, BMI, regular menstrual cycle, parity, age at first birth, time since OCP use, presence of endocrine disorders, family history of breast cancer and other hormones and SHBG; and corrected for regression dilution using repeat measures except for total and calculated free oestradiol.
Fig. 3
Fig. 3. Associations of total and calculated free oestradiol with the risk of invasive breast cancer by phase of the menstrual cycle in pre-menopausal women.
Hazard ratios stratified for age group, region and deprivation; and adjusted for age (underlying time variable), ethnicity, educational level, smoking, alcohol, physical activity, BMI, regular menstrual cycle, parity, age at first birth, time since OCP use, presence of endocrine disorders, family history of breast cancer and other hormones and SHBG.
Fig. 4
Fig. 4. Geometric mean concentrations of total oestradiol by phase of the menstrual cycle in pre-menopausal women.
Menstrual cycle phases were defined by forward dating as early follicular = days 0–5, late follicular = days 6–10, mid-cycle = days 11–14, early luteal = days 15–18, mid-luteal = days 19–24 and late luteal = days ≥25.
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