1. Advanced glycation end products are elevated in estrogen receptor-positive breast cancer patients, alter response to therapy, and can be targeted by lifestyle intervention.
- Author
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Walter KR, Ford ME, Gregoski MJ, Kramer RM, Knight KD, Spruill L, Nogueira LM, Krisanits BA, Phan V, La Rue AC, Lilly MB, Ambs S, Chan K, Turner TF, Varner H, Singh S, Uribarri J, Garrett-Mayer E, Armeson KE, Hilton EJ, Clair MJ, Taylor MH, Abbott AM, Findlay VJ, Peterson LL, Magwood G, and Turner DP
- Subjects
- Aged, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal therapeutic use, Biomarkers, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Cancer Survivors, Cell Line, Tumor, Combined Modality Therapy, Drug Resistance, Neoplasm, Female, Glycation End Products, Advanced blood, Humans, Middle Aged, Neoplasm Grading, Neoplasm Staging, Risk Factors, Signal Transduction drug effects, Tamoxifen administration & dosage, Tamoxifen therapeutic use, Treatment Outcome, Breast Neoplasms metabolism, Breast Neoplasms pathology, Glycation End Products, Advanced metabolism, Life Style, Receptors, Estrogen metabolism
- 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.
- Published
- 2019
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