Dietary Advanced Glycation End-Products and Mortality after Breast Cancer in the Women’s Health Initiative

Background: Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary N^e-carboxymethyl-lysine (CML)–AGE intake and mortality among women diagnosed with breast cancer. Methods: Postmenopausal women aged 50 to 79 years were enrolled in the Women’s Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease. Results: After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer–related, and 129 were cardiovascular disease–related). Postdiagnosis CML-AGE intake was associated with all-cause (HR_T3vsT1, 1.37; 95% CI, 1.09–1.74), breast cancer (HR_T3vsT1, 1.49; 95% CI, 0.98–2.24), and cardiovascular disease (HR_T3vsT1, 1.91; 95% CI, 1.09–3.32) mortality. Conclusions: Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer. Impact: Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.