Composite measures of lifetime endogenous oestrogen exposure and breast cancer risk — The Association Specialists
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  3. Composite measures of lifetime endogenous oestrogen exposure and breast cancer risk

Composite measures of lifetime endogenous oestrogen exposure and breast cancer risk (23870)

Xiaowen Liu 1 , Zhoufeng Ye 1 , Tuong L Nguyen 1 , Shuai Li 1 , On behalf of BCAC 2
  1. Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia
  2. Breast Cancer Association Consortium, Cambridge, UK

Background
Breast cancer risk is influenced by complex hormonal and reproductive exposures. Breast tissue age (BTA) and lifetime endogenous estrogen exposure measure (LEOEM) have been developed to integrate major reproductive factors and reflect cumulative endogenous oestrogen exposure. This study aimed to investigate the associations of BTA and LEOEM with breast cancer and subtypes, and assess association modification by established and putative risk factors.

Methods
BTA and LEOEM were calculated for 30,224 breast cancer cases and 29,887 controls from 19 countries from the Breast Cancer Association Consortium (BCAC). Logistic regression was used to estimate odds ratios per adjusted standard deviation (OPERA) for BTA and LEOEM. Association modification was evaluated by stratified analyses and heterogeneity test between strata.

Results
BTA [OPERA = 1.10; 95% confidence interval (CI): 1.09, 1.12] demonstrated a stronger risk gradient with breast cancer than LEOEM (OPERA = 1.05; 95% CI: 1.04, 1.07) and any individual reproductive factor. Stratified analyses revealed LEOEM exhibited stronger associations for premenopausal women (OPERA = 1.32; 95% CI: 1.22, 1.43) and early-onset cancer diagnosed before 45 years (OPERA = 1.25; 95% CI: 1.14, 1.38), whereas BTA showed a slightly greater effect size in late-onset cases (OPERA = 1.14; 95% CI: 1.12, 1.16). Regarding subtypes, LEOEM was exclusively associated with ER-positive cases, whereas BTA demonstrated an association across subtypes, which was notably more pronounced in ER-positive (OPERA = 1.13; 95% CI: 1.10, 1.15) than ER-negative disease (OPERA = 1.04; 95% CI: 1.01, 1.07).

Conclusions
Composite measures of lifetime endogenous oestrogen exposure provide more informative and biologically coherent risk stratification than individual reproductive factors. Specifically, LEOEM better captures early-onset and ER-positive breast cancer risk, while BTA is more relevant for older women and both ER-subtypes. Derived from routinely collected reproductive history, the two measures hold potential to enhance individualized prevention and screening strategies in clinical practice.