Advanced glycation end products are elevated in estrogen receptor-positive breast cancer patients, alter response to therapy, and can be targeted by lifestyle intervention

Abstract

Purpose Lifestyle factors associated with personal behavior can alter tumor-associated biological pathways and thereby increase cancer risk, growth, and disease recurrence. Advanced glycation end products (AGEs) are reactive metabolites produced endogenously as a by-product of normal metabolism. A Western lifestyle also promotes AGE accumulation in the body which is associated with disease phenotypes through modification of the genome, protein crosslinking/dysfunction, and aberrant cell signaling. Given the links between lifestyle, AGEs, and disease, we examined the association between dietary-AGEs and breast cancer. Methods We evaluated AGE levels in bio-specimens from estrogen receptor-positive (ER+) and estrogen receptor-negative (ER−) breast cancer patients, examined their role in therapy resistance, and assessed the ability of lifestyle intervention to reduce circulating AGE levels in ER+ breast cancer survivors. Results An association between ER status and AGE levels was observed in tumor and serum samples. AGE treatment of ER+ breast cancer cells altered ERα phosphorylation and promoted resistance to tamoxifen therapy. In a proof of concept study, physical activity and dietary intervention was shown to be viable options for reducing circulating AGE levels in breast cancer survivors. Conclusions There is a potential prognostic and therapeutic role for lifestyle derived AGEs in breast cancer. Given the potential benefits of lifestyle intervention on incidence and mortality, opportunities exist for the development of community health and nutritional programs aimed at reducing AGE exposure in order to improve breast cancer prevention and treatment outcomes. Electronic supplementary material The online version of this article (10.1007/s10549-018-4992-7) contains supplementary material, which is available to authorized users.

Reply to letter to the editor: “Advanced glycation end‐products and their receptors: Exercise effects”

“…3 In their letter, Kotani and Gugliucci searched and compiled data from interventional studies in which the effects of physical exercise on AGEs and soluble AGEs receptors (sRAGE) were evaluated. [4][5][6][7][8][9][10] Based on those studies, the authors concluded that the practice of physical exercise could reduce serum AGEs and, seemingly contradictory, it also reduces sRAGE concentrations. 1 However, we would advert caution before drawing these conclusions.…”

“…Conversely, in two papers, there is no mention about participants smoking status, 5,10 and dietary AGEs intake were only quantified in two studies. 4,5 In the study conducted by Walter et al, the intervention consisted of 11-week physical activity programme and dietary counselling. 5 Dietary AGEs intake was assessed before and after the intervention, based on a 7-day food record.…”

“…4,5 In the study conducted by Walter et al, the intervention consisted of 11-week physical activity programme and dietary counselling. 5 Dietary AGEs intake was assessed before and after the intervention, based on a 7-day food record. Besides the reduction in serum AGEs, the authors also observed a lower dietary AGEs intake.…”

“…Besides the reduction in serum AGEs, the authors also observed a lower dietary AGEs intake. 5 In a randomized controlled parallel trial, 43 healthy overweight or obese men were assigned to one of three groups: low-AGE diet, exercise with habitual dietary intake, or exercise plus low AGE diet. 4 Interestingly, in the exercise with habitual dietary intake group, concentrations of AGEs remained unchanged after the intervention period.…”

Advanced glycation end‐products and their receptors: Exercise effects

“…Two reports (including one report of a randomized control trial [RCT]) with a diet and exercise intervention 2,3 and five reports (including one RCT) with an exercise intervention 4-8 were selected (Table 1). Except for two studies, 3,7 the intervention produced significant weight loss. [4][5][6] Five studies measured the AGEs levels, which demonstrated significant reductions by a diet and exercise intervention 2,3 and an exercise intervention.…”