TY - JOUR
T1 - Advanced glycation end products are elevated in estrogen receptor-positive breast cancer patients, alter response to therapy, and can be targeted by lifestyle intervention
AU - Walter, Katherine R.
AU - Ford, Marvella E.
AU - Gregoski, Mathew J.
AU - Kramer, Rita M.
AU - Knight, Kendrea D.
AU - Spruill, Laura
AU - Nogueira, Lourdes M.
AU - Krisanits, Bradley A.
AU - Phan, Van
AU - La Rue, Amanda C.
AU - Lilly, Michael B.
AU - Ambs, Stefan
AU - Chan, King
AU - Turner, Tonya F.
AU - Varner, Heidi
AU - Singh, Shweta
AU - Uribarri, Jaime
AU - Garrett-Mayer, Elizabeth
AU - Armeson, Kent E.
AU - Hilton, Ebony J.
AU - Clair, Mark J.
AU - Taylor, Marian H.
AU - Abbott, Andrea M.
AU - Findlay, Victoria J.
AU - Peterson, Lindsay L.
AU - Magwood, Gayenell
AU - Turner, David P.
N1 - Funding Information:
Fig. 4 Lifestyle intervention reduces the levels of AGE in the circulation of ER+ breast cancer survivors. a Circulatory AGE levels per participant at baseline, week 8 and week 11 of the lifestyle intervention as assessed by ELISA. b Average AGE levels at baseline, weeks 8 and 11 for all participants of the lifestyle intervention as assessed by ELISA. c Percent change in circulating AGE levels at baseline, weeks 8 and 11 for all participants at of the lifestyle intervention and 13 weeks after the intervention had ended as assessed by ELISA. d Aver age IL6 levels at baseline and at completion for all partici pants of the 11-week lifestyle intervention as assessed by ELISA. e Average CRP levels at baseline and at completion for all participants of the 11-week lifestyle intervention as assessed by ELISA Acknowledgements Supported in part by Jill and John Chalsty; the Biostatistics Shared Resource, the Biorepository Shared Resource, Hollings Cancer Center, and pilot research funding, Hollings Cancer Center’s Cancer Center Support Grant P30 CA138313 at the Medical University of South Carolina.
Funding Information:
Funding This work was/is supported by grants from the NIH/NCI, P20 CA157071 & U54 CA210962 to M.E. Ford; R21 CA176135 to D.P. Turner.
Funding Information:
Supported in part by Jill and John Chalsty; the Biostatistics Shared Resource, the Biorepository Shared Resource, Hollings Cancer Center, and pilot research funding, Hollings Cancer Center?s Cancer Center Support Grant P30 CA138313 at the Medical University of South Carolina.
Publisher Copyright:
© 2018, The Author(s).
PY - 2019/2/15
Y1 - 2019/2/15
N2 - 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.
AB - 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.
KW - Advanced glycation end product
KW - Breast cancer
KW - Estrogen receptor
KW - Lifestyle intervention
KW - Tamoxifen resistance
UR - http://www.scopus.com/inward/record.url?scp=85055882137&partnerID=8YFLogxK
U2 - 10.1007/s10549-018-4992-7
DO - 10.1007/s10549-018-4992-7
M3 - Article
C2 - 30368741
AN - SCOPUS:85055882137
SN - 0167-6806
VL - 173
SP - 559
EP - 571
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -