Obesity and Breast Cancer: Molecular and Epidemiological Evidence

Authors

  • Nehad M. Ayoub Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
  • Amal Kaddoumi Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71201, USA

DOI:

https://doi.org/10.6000/1929-2279.2015.04.01.3

Keywords:

Adipokines, Obesity, Leptin, Adiponectin, Visfatin, Inflammation.

Abstract

 Carcinoma of the breast is a leading cause of cancer deaths among women world-wide. Obesity is recognized as a well-established risk factor for epithelial tumors including the mammary epithelium. Adipose tissue is considered to be metabolically active organ with the ability to secrete a wide range of biologically active adipokines. Multiple studies have evaluated the potential mechanisms correlating obesity to increased risk of breast cancer. Altered circulating levels of adipokines or changed adipokine signaling pathways are now increasingly recognized to be associated with breast cancer development and progression. Leptin and adiponectin were the main adipokines that have been investigated in the context of breast cancer in both preclinical and epidemiological studies. Obesity is also believed to promote inflammatory response and induce activity of key enzymes like aromatase, leading to higher risk of breast cancer development. The goal of this review is to provide recent insights into the potential molecular mechanisms linking adipokines to the etiopathogenesis of breast cancer including recently identified adipokines and trying to correlate these molecular mechanisms to more established metabolic and hormonal dysregulations of obesity. A better understanding of the interplay between adipokines and other deregulated mechanisms in obesity is important for the development of preventive strategies with therapeutic potential against breast cancer in obese patients.

References

Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29. http://dx.doi.org/10.3322/caac.21208

Petekkaya I, Sahin U, Gezgen G, et al. Association of breast cancer subtypes and body mass index. Tumori 2013; 99: 129-33.

Minatoya M, Kutomi G, Asakura S, et al. Equol, adiponectin, insulin levels and risk of breast cancer. Asian Pac J Cancer Prev 2013; 14: 2191-9. http://dx.doi.org/10.7314/APJCP.2013.14.4.2191

Mehta R, Katta H, Alimirah F, et al. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells. PLoS One 2013; 8: e65113.

Alegre MM, Knowles MH, Robison RA, O'Neill KL. Mechanics behind breast cancer prevention - focus on obesity, exercise and dietary fat. Asian Pac J Cancer Prev 2013; 14: 2207-12. http://dx.doi.org/10.7314/APJCP.2013.14.4.2207

Kaviani A, Neishaboury M, Mohammadzadeh N, Ansari-Damavandi M, Jamei K. Effects of obesity on presentation of breast cancer, lymph node metastasis and patient survival: a retrospective review. Asian Pac J Cancer Prev 2013; 14: 2225-9. http://dx.doi.org/10.7314/APJCP.2013.14.4.2225

Ademuyiwa FO, Groman A, O'Connor T, Ambrosone C, Watroba N, Edge SB. Impact of body mass index on clinical outcomes in triple-negative breast cancer. Cancer 2011; 117: 4132-40. http://dx.doi.org/10.1002/cncr.26019

Abdel-Maksoud MF, Risendal BC, Slattery ML, Giuliano AR, Baumgartner KB, Byers TE. Behavioral risk factors and their relationship to tumor characteristics in Hispanic and non-Hispanic white long-term breast cancer survivors. Breast Cancer Res Treat 2012; 131: 169-76. http://dx.doi.org/10.1007/s10549-011-1705-x

Hursting SD, Hursting MJ. Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer. Arterioscler Thromb Vasc Biol 2012; 32: 1766-70. http://dx.doi.org/10.1161/ATVBAHA.111.241927

Haakinson DJ, Leeds SG, Dueck AC, et al. The impact of obesity on breast cancer: a retrospective review. Ann Surg Oncol 2012; 19: 3012-8. http://dx.doi.org/10.1245/s10434-012-2320-8

Sparano JA, Wang M, Zhao F, et al. Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer 2012; 118: 5937-46. http://dx.doi.org/10.1002/cncr.27527

Moore T, Beltran L, Carbajal S, Hursting SD, DiGiovanni J. Energy balance modulates mouse skin tumor promotion through altered IGF-1R and EGFR crosstalk. Cancer Prev Res (Phila) 2012; 5: 1236-46. http://dx.doi.org/10.1158/1940-6207.CAPR-12-0234

Anderson GL, Neuhouser ML. Obesity and the risk for premenopausal and postmenopausal breast cancer. Cancer Prev Res (Phila) 2012; 5: 515-21. http://dx.doi.org/10.1158/1940-6207.CAPR-12-0091

Fiorio E, Mercanti A, Terrasi M, et al. Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis. BMC Cancer 2008; 8: 305. http://dx.doi.org/10.1186/1471-2407-8-305

Vona-Davis L, Rose DP, Hazard H, et al. Triple-negative breast cancer and obesity in a rural Appalachian population. Cancer Epidemiol Biomarkers Prev 2008; 17: 3319-24. http://dx.doi.org/10.1158/1055-9965.EPI-08-0544

Dubois V, Delort L, Billard H, Vasson MP, Caldefie-Chezet F. Breast cancer and obesity: in vitro interferences between adipokines and proangiogenic features and/or antitumor therapies? PLoS One 2013; 8: e58541.

Kamineni A, Anderson ML, White E, et al. Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population. Cancer Causes Control 2013; 24: 305-12. http://dx.doi.org/10.1007/s10552-012-0115-7

Gillespie EF, Sorbero ME, Hanauer DA, et al. Obesity and angiolymphatic invasion in primary breast cancer. Ann Surg Oncol 2010; 17: 752-9. http://dx.doi.org/10.1245/s10434-009-0797-6

Fuentes-Mattei E, Velazquez-Torres G, Phan L, et al. Effects of obesity on transcriptomic changes and cancer hallmarks in estrogen receptor-positive breast cancer. J Natl Cancer Inst 2014; 106.

Ray A, Nkhata KJ, Cleary MP. Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. Int J Oncol 2007; 30: 1499-509.

Cleary MP. Impact of obesity on development and progression of mammary tumors in preclinical models of breast cancer. J Mammary Gland Biol Neoplasia 2013; 18: 333-43. http://dx.doi.org/10.1007/s10911-013-9300-x

Mandelblatt J, van Ravesteyn N, Schechter C, et al. Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention. Cancer 2013; 119: 2541-8. http://dx.doi.org/10.1002/cncr.28087

Biglia N, Peano E, Sgandurra P, et al. Body mass index (BMI) and breast cancer: impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women. Gynecol Endocrinol 2013; 29: 263-7. http://dx.doi.org/10.3109/09513590.2012.736559

Xing P, Li JG, Jin F, et al. Prognostic significance of body mass index in breast cancer patients with hormone receptor-positive tumours after curative surgery. Clin Invest Med 2013; 36: E297-305.

Keskin O, Aksoy S, Babacan T, et al. Impact of the obesity on lymph node status in operable breast cancer patients. J BUON 2013; 18: 824-30.

Arendt LM, McCready J, Keller PJ, et al. Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis. Cancer Res 2013; 73: 6080-93. http://dx.doi.org/10.1158/0008-5472.CAN-13-0926

Chen S, Chen CM, Zhou Y, Zhou RJ, Yu KD, Shao ZM. Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer. PLoS One 2012; 7: e41380. http://dx.doi.org/10.1371/journal.pone.0041380

Turkoz FP, Solak M, Petekkaya I, et al. The prognostic impact of obesity on molecular subtypes of breast cancer in premenopausal women. J BUON 2013; 18: 335-41.

Amadou A, Ferrari P, Muwonge R, et al. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis. Obes Rev 2013; 14: 665-78. http://dx.doi.org/10.1111/obr.12028

Cheraghi Z, Poorolajal J, Hashem T, Esmailnasab N, Doosti Irani A. Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis. PLoS One 2012; 7: e51446. http://dx.doi.org/10.1371/journal.pone.0051446

Liedtke S, Schmidt ME, Vrieling A, et al. Postmenopausal sex hormones in relation to body fat distribution. Obesity (Silver Spring) 2012; 20: 1088-95. http://dx.doi.org/10.1038/oby.2011.383

Fagherazzi G, Chabbert-Buffet N, Fabre A, et al. Hip circumference is associated with the risk of premenopausal ER-/PR- breast cancer. Int J Obes (Lond) 2012; 36: 431-9. http://dx.doi.org/10.1038/ijo.2011.66

Pinheiro RL, Sarian LO, Pinto-Neto AM, Morais S, Costa-Paiva L. Relationship between body mass index, waist circumference and waist to hip ratio and the steroid hormone receptor status in breast carcinoma of pre- and postmenopausal women. Breast 2009; 18: 8-12. http://dx.doi.org/10.1016/j.breast.2008.09.001

McColl KE. Serum IGF-1 linking visceral obesity with esophageal adenocarcinoma: unconvincing evidence. Am J Gastroenterol 2012; 107: 205-6. http://dx.doi.org/10.1038/ajg.2011.421

Delort L, Jarde T, Dubois V, Vasson MP, Caldefie-Chezet F. New insights into anticarcinogenic properties of adiponectin: a potential therapeutic approach in breast cancer? Vitam Horm 2012; 90: 397-417. http://dx.doi.org/10.1016/B978-0-12-398313-8.00015-4

Gross AL, Newschaffer CJ, Hoffman-Bolton J, Rifai N, Visvanathan K. Adipocytokines, inflammation, and breast cancer risk in postmenopausal women: a prospective study. Cancer Epidemiol Biomarkers Prev 2013; 22: 1319-24. http://dx.doi.org/10.1158/1055-9965.EPI-12-1444

Khan M, Joseph F. Adipose tissue and adipokines: the association with and application of adipokines in obesity. Scientifica (Cairo) 2014; 2014: 328592.

Izadi V, Saraf-Bank S, Azadbakht L. Dietary intakes and leptin concentrations. ARYA Atheroscler 2014; 10: 266-72.

Romero-Figueroa Mdel S, Garduno-Garcia Jde J, Duarte-Mote J, Matute-Gonzalez G, Gomez-Villanueva A, De la Cruz-Vargas J. Insulin and leptin levels in obese patients with and without breast cancer. Clin Breast Cancer 2013; 13: 482-5. http://dx.doi.org/10.1016/j.clbc.2013.08.001

Mohammadzadeh G, Ghaffari MA, Bafandeh A, Hosseini SM. Effect of leptin receptor Q223R polymorphism on breast cancer risk. Iran J Basic Med Sci 2014; 17: 588-94.

Terrasi M, Bazan V, Caruso S, et al. Effects of PPARgamma agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells. J Cell Physiol 2013; 228: 1368-74. http://dx.doi.org/10.1002/jcp.24295

Napoleone E, Cutrone A, Cugino D, et al. Leptin upregulates tissue factor expression in human breast cancer MCF-7 cells. Thromb Res 2012; 129: 641-7. http://dx.doi.org/10.1016/j.thromres.2011.07.037

Ren H, Zhao T, Wang X, et al. Leptin upregulates telomerase activity and transcription of human telomerase reverse transcriptase in MCF-7 breast cancer cells. Biochem Biophys Res Commun 2010; 394: 59-63. http://dx.doi.org/10.1016/j.bbrc.2010.02.093

Khanal T, Kim HG, Do MT, et al. Leptin induces CYP1B1 expression in MCF-7 cells through ligand-independent activation of the ERalpha pathway. Toxicol Appl Pharmacol 2014; 277: 39-48. http://dx.doi.org/10.1016/j.taap.2014.03.003

Chen X, Zha X, Chen W, et al. Leptin attenuates the anti-estrogen effect of tamoxifen in breast cancer. Biomed Pharmacother 2013; 67: 22-30. http://dx.doi.org/10.1016/j.biopha.2012.10.001

Dubois V, Jarde T, Delort L, et al. Leptin induces a proliferative response in breast cancer cells but not in normal breast cells. Nutr Cancer 2014; 66: 645-55. http://dx.doi.org/10.1080/01635581.2014.894104

Morad V, Abrahamsson A, Dabrosin C. Estradiol affects extracellular leptin: adiponectin ratio in human breast tissue in vivo. J Clin Endocrinol Metab 2014; 99: 3460-7. http://dx.doi.org/10.1210/jc.2014-1129

Battle M, Gillespie C, Quarshie A, et al. Obesity induced a leptin-Notch signaling axis in breast cancer. Int J Cancer 2014; 134: 1605-16. http://dx.doi.org/10.1002/ijc.28496

Yan D, Avtanski D, Saxena NK, Sharma D. Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires beta-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. J Biol Chem 2012; 287: 8598-612. http://dx.doi.org/10.1074/jbc.M111.322800

Liu C, Liu L. Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: a meta-analysis. Tumour Biol 2011; 32: 1233-40. http://dx.doi.org/10.1007/s13277-011-0227-9

Cleveland RJ, Gammon MD, Long CM, et al. Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival. Breast Cancer Res Treat 2010; 120: 745-52. http://dx.doi.org/10.1007/s10549-009-0503-1

Terrasi M, Fiorio E, Mercanti A, et al. Functional analysis of the -2548G/A leptin gene polymorphism in breast cancer cells. Int J Cancer 2009; 125: 1038-44. http://dx.doi.org/10.1002/ijc.24372

Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 2007; 14: 189-206. http://dx.doi.org/10.1677/ERC-06-0068

Harris HR, Tworoger SS, Hankinson SE, Rosner BA, Michels KB. Plasma leptin levels and risk of breast cancer in premenopausal women. Cancer Prev Res (Phila) 2011; 4: 1449-56. http://dx.doi.org/10.1158/1940-6207.CAPR-11-0125

Rose DP, Vona-Davis L. Biochemical and molecular mechanisms for the association between obesity, chronic inflammation, and breast cancer. Biofactors 2014; 40: 1-12. http://dx.doi.org/10.1002/biof.1109

Grossmann ME, Cleary MP. The balance between leptin and adiponectin in the control of carcinogenesis - focus on mammary tumorigenesis. Biochimie 2012; 94: 2164-71. http://dx.doi.org/10.1016/j.biochi.2012.06.013

Giordano C, Vizza D, Panza S, et al. Leptin increases HER2 protein levels through a STAT3-mediated up-regulation of Hsp90 in breast cancer cells. Mol Oncol 2013; 7: 379-91. http://dx.doi.org/10.1016/j.molonc.2012.11.002

Catalano S, Mauro L, Bonofiglio D, et al. In vivo and in vitro evidence that PPARgamma ligands are antagonists of leptin signaling in breast cancer. Am J Pathol 2011; 179: 1030-40. http://dx.doi.org/10.1016/j.ajpath.2011.04.026

Obeid S, Hebbard L. Role of adiponectin and its receptors in cancer. Cancer Biol Med 2012; 9: 213-20.

Otvos L, Jr., Haspinger E, La Russa F, et al. Design and development of a peptide-based adiponectin receptor agonist for cancer treatment. BMC Biotechnol 2011; 11: 90. http://dx.doi.org/10.1186/1472-6750-11-90

Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res 2005; 28: 1263-9. http://dx.doi.org/10.1007/BF02978210

Wang Y, Lam JB, Lam KS, et al. Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res 2006; 66: 11462-70. http://dx.doi.org/10.1158/0008-5472.CAN-06-1969

Taliaferro-Smith L, Nagalingam A, Zhong D, Zhou W, Saxena NK, Sharma D. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene 2009; 28: 2621-33. http://dx.doi.org/10.1038/onc.2009.129

Dos Santos E, Benaitreau D, Dieudonne MN, et al. Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells. Oncol Rep 2008; 20: 971-7.

Liu J, Xu A, Lam KS, et al. Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation. Oncotarget 2013; 4: 1804-18.

Hou WK, Xu YX, Yu T, et al. Adipocytokines and breast cancer risk. Chin Med J (Engl) 2007; 120: 1592-6.

Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res 2003; 9: 5699-704.

Macis D, Guerrieri-Gonzaga A, Gandini S. Circulating adiponectin and breast cancer risk: a systematic review and meta-analysis. Int J Epidemiol 2014; 43: 1226-36. http://dx.doi.org/10.1093/ije/dyu088

Minatoya M, Kutomi G, Shima H, et al. Relation of serum adiponectin levels and obesity with breast cancer: a Japanese case-control study. Asian Pac J Cancer Prev 2014; 15: 8325-30. http://dx.doi.org/10.7314/APJCP.2014.15.19.8325

Panis C, Herrera AC, Aranome AM, et al. Clinical insights from adiponectin analysis in breast cancer patients reveal its anti-inflammatory properties in non-obese women. Mol Cell Endocrinol 2014; 382: 190-6. http://dx.doi.org/10.1016/j.mce.2013.09.030

Cubukcu E, Olmez OF, Kanat O, et al. Lack of prognostic significance of adiponectin immunohistochemical expression in patients with triple-negative breast cancer. Contemp Oncol (Pozn) 2014; 18: 34-8.

Kaklamani VG, Hoffmann TJ, Thornton TA, et al. Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women's Health Initiative. Breast Cancer Res Treat 2013; 139: 461-8. http://dx.doi.org/10.1007/s10549-013-2546-6

Lim S, Quon MJ, Koh KK. Modulation of adiponectin as a potential therapeutic strategy. Atherosclerosis 2014; 233: 721-8. http://dx.doi.org/10.1016/j.atherosclerosis.2014.01.051

Abella V, Scotece M, Conde J, et al. Adipokines, metabolic syndrome and rheumatic diseases. J Immunol Res 2014; 2014: 343746. http://dx.doi.org/10.1155/2014/343746

Kim JG, Kim EO, Jeong BR, et al. Visfatin stimulates proliferation of MCF-7 human breast cancer cells. Mol Cells 2010; 30: 341-5. http://dx.doi.org/10.1007/s10059-010-0124-x

Lee YC, Yang YH, Su JH, Chang HL, Hou MF, Yuan SS. High visfatin expression in breast cancer tissue is associated with poor survival. Cancer Epidemiol Biomarkers Prev 2011; 20: 1892-901. http://dx.doi.org/10.1158/1055-9965.EPI-11-0399

Soncini D, Caffa I, Zoppoli G, et al. Nicotinamide phosphoribosyltransferase promotes epithelial-to-mesenchymal transition as a soluble factor independent of its enzymatic activity. J Biol Chem 2014. http://dx.doi.org/10.1074/jbc.M114.594721

Park HJ, Kim SR, Kim SS, et al. Visfatin promotes cell and tumor growth by upregulating Notch1 in breast cancer. Oncotarget 2014; 5: 5087-99.

Li XY, Tang SH, Zhou XC, Ye YH, Xu XQ, Li RZ. Preoperative serum visfatin levels and prognosis of breast cancer among Chinese women. Peptides 2014; 51: 86-90. http://dx.doi.org/10.1016/j.peptides.2013.11.010

Dalamaga M, Karmaniolas K, Papadavid E, Pelekanos N, Sotiropoulos G, Lekka A. Elevated serum visfatin/nicotinamide phosphoribosyl-transferase levels are associated with risk of postmenopausal breast cancer independently from adiponectin, leptin, and anthropometric and metabolic parameters. Menopause 2011; 18: 1198-204. http://dx.doi.org/10.1097/gme.0b013e31821e21f5

Dalamaga M. Nicotinamide phosphoribosyl-transferase/visfatin: a missing link between overweight/obesity and postmenopausal breast cancer? Potential preventive and therapeutic perspectives and challenges. Med Hypotheses 2012; 79: 617-21. http://dx.doi.org/10.1016/j.mehy.2012.07.036

Kim SR, Park HJ, Bae YH, et al. Curcumin down-regulates visfatin expression and inhibits breast cancer cell invasion. Endocrinology 2012; 153: 554-63. http://dx.doi.org/10.1210/en.2011-1413

Bajrami I, Kigozi A, Van Weverwijk A, et al. Synthetic lethality of PARP and NAMPT inhibition in triple-negative breast cancer cells. EMBO Mol Med 2012; 4: 1087-96. http://dx.doi.org/10.1002/emmm.201201250

Sun CA, Wu MH, Chu CH, et al. Adipocytokine resistin and breast cancer risk. Breast Cancer Res Treat 2010; 123: 869-76. http://dx.doi.org/10.1007/s10549-010-0792-4

Wedrychowicz A, Zajac A, Pilecki M, Koscielniak B, Tomasik PJ. Peptides from adipose tissue in mental disorders. World J Psychiatry 2014; 4: 103-11. http://dx.doi.org/10.5498/wjp.v4.i4.103

Stojsavljevic S, Gomercic Palcic M, Virovic Jukic L, Smircic Duvnjak L, Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20: 18070-91. http://dx.doi.org/10.3748/wjg.v20.i48.18070

Stewart PA, Luks J, Roycik MD, Sang QX, Zhang J. Differentially expressed transcripts and dysregulated signaling pathways and networks in African American breast cancer. PLoS One 2013; 8: e82460. http://dx.doi.org/10.1371/journal.pone.0082460

Lee YC, Chen YJ, Wu CC, Lo S, Hou MF, Yuan SS. Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification. Gynecol Oncol 2012; 125: 742-50. http://dx.doi.org/10.1016/j.ygyno.2012.02.032

Tsai CH, Tsai HC, Huang HN, et al. Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells. Oncotarget 2014.

Hsieh YY, Shen CH, Huang WS, et al. Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFkappaB signaling pathway in gastric cancer cells. J Biomed Sci 2014; 21: 59. http://dx.doi.org/10.1186/1423-0127-21-59

Kim HJ, Lee YS, Won EH, et al. Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation. BJU Int 2011; 108: E77-83. http://dx.doi.org/10.1111/j.1464-410X.2010.09813.x

Dalamaga M, Karmaniolas K, Papadavid E, Pelekanos N, Sotiropoulos G, Lekka A. Hyperresistinemia is associated with postmenopausal breast cancer. Menopause 2013; 20: 845-51. http://dx.doi.org/10.1097/GME.0b013e31827f06dc

Alokail MS, Al-Daghri N, Abdulkareem A, et al. Metabolic syndrome biomarkers and early breast cancer in Saudi women: evidence for the presence of a systemic stress response and/or a pre-existing metabolic syndrome-related neoplasia risk? BMC Cancer 2013; 13: 54. http://dx.doi.org/10.1186/1471-2407-13-54

Kang JH, Yu BY, Youn DS. Relationship of serum adiponectin and resistin levels with breast cancer risk. J Korean Med Sci 2007; 22: 117-21. http://dx.doi.org/10.3346/jkms.2007.22.1.117

Kawaguchi M, Kataoka H. Mechanisms of hepatocyte growth factor activation in cancer tissues. Cancers (Basel) 2014; 6: 1890-904. http://dx.doi.org/10.3390/cancers6041890

You WK, McDonald DM. The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep 2008; 41: 833-9. http://dx.doi.org/10.5483/BMBRep.2008.41.12.833

Kirchhofer D, Yao X, Peek M, et al. Structural and functional basis of the serine protease-like hepatocyte growth factor beta-chain in Met binding and signaling. J Biol Chem 2004; 279: 39915-24. http://dx.doi.org/10.1074/jbc.M404795200

Stein GY, Yosef N, Reichman H, et al. Met kinetic signature derived from the response to HGF/SF in a cellular model predicts breast cancer patient survival. PLoS One 2012; 7: e45969. http://dx.doi.org/10.1371/journal.pone.0045969

Locatelli A, Lofgren KA, Daniel AR, Castro NE, Lange CA. Mechanisms of HGF/Met signaling to Brk and Sam68 in breast cancer progression. Horm Cancer 2012; 3: 14-25. http://dx.doi.org/10.1007/s12672-011-0097-z

Rehman J, Traktuev D, Li J, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 2004; 109: 1292-8. http://dx.doi.org/10.1161/01.CIR.0000121425.42966.F1

Faber DR, Moll FL, Vink A, et al. Adipose tissue quantity and composition contribute to adipokine concentrations in the subclavian vein and the inferior mesenteric vein. Int J Obes (Lond) 2012; 36: 1078-85. http://dx.doi.org/10.1038/ijo.2011.214

D'Esposito V, Passaretti F, Hammarstedt A, et al. Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro. Diabetologia 2012; 55: 2811-22. http://dx.doi.org/10.1007/s00125-012-2629-7

Rehman J, Considine RV, Bovenkerk JE, et al. Obesity is associated with increased levels of circulating hepatocyte growth factor. J Am Coll Cardiol 2003; 41: 1408-13. http://dx.doi.org/10.1016/S0735-1097(03)00231-6

Tang Z, Du R, Jiang S, et al. Dual MET-EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer. Br J Cancer 2008; 99: 911-22. http://dx.doi.org/10.1038/sj.bjc.6604559

Sattler M, Salgia R. The MET axis as a therapeutic target. Update Cancer Ther 2009; 3: 109-18. http://dx.doi.org/10.1016/j.uct.2009.01.001

Lawrence RE, Salgia R. MET molecular mechanisms and therapies in lung cancer. Cell Adh Migr 2010; 4: 146-52. http://dx.doi.org/10.4161/cam.4.1.10973

Sundaram S, Freemerman AJ, Johnson AR, et al. Role of HGF in obesity-associated tumorigenesis: C3(1)-TAg mice as a model for human basal-like breast cancer. Breast Cancer Res Treat 2013; 142: 489-503. http://dx.doi.org/10.1007/s10549-013-2741-5

Sundaram S, Le TL, Essaid L, et al. Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression. Front Oncol 2014; 4: 175. http://dx.doi.org/10.3389/fonc.2014.00175

Sundaram S, Freemerman AJ, Galanko JA, et al. Obesity-Mediated Regulation of HGF/c-Met Is Associated with Reduced Basal-Like Breast Cancer Latency in Parous Mice. PLoS One 2014; 9: e111394. http://dx.doi.org/10.1371/journal.pone.0111394

Chen H, Zhang ZW, Guo Y, et al. The proliferative role of insulin and the mechanism underlying this action in human breast cancer cell line MCF-7. J BUON 2012; 17: 658-62.

Bartella V, Cascio S, Fiorio E, Auriemma A, Russo A, Surmacz E. Insulin-dependent leptin expression in breast cancer cells. Cancer Res 2008; 68: 4919-27. http://dx.doi.org/10.1158/0008-5472.CAN-08-0642

Garofalo C, Koda M, Cascio S, et al. Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli. Clin Cancer Res 2006; 12: 1447-53. http://dx.doi.org/10.1158/1078-0432.CCR-05-1913

Belardi V, Gallagher EJ, Novosyadlyy R, LeRoith D. Insulin and IGFs in obesity-related breast cancer. J Mammary Gland Biol Neoplasia 2013; 18: 277-89. http://dx.doi.org/10.1007/s10911-013-9303-7

Hvidtfeldt UA, Gunter MJ, Lange T, et al. Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption, and breast cancer. Cancer Epidemiol Biomarkers Prev 2012; 21: 1203-12. http://dx.doi.org/10.1158/1055-9965.EPI-12-0310

Gunter MJ, Hoover DR, Yu H, et al. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 2009; 101: 48-60. http://dx.doi.org/10.1093/jnci/djn415

Can A, Alacacioglu A, Kucukzeybek Y, et al. The relationship of insulin resistance and metabolic syndrome with known breast cancer prognostic factors in postmenopausal breast cancer patients. J BUON 2013; 18: 845-50.

Minicozzi P, Berrino F, Sebastiani F, et al. High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease. Eur J Cancer 2013; 49: 3881-8. http://dx.doi.org/10.1016/j.ejca.2013.08.004

Duggan C, Irwin ML, Xiao L, et al. Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol 2011; 29: 32-9. http://dx.doi.org/10.1200/JCO.2009.26.4473

Sieri S, Muti P, Claudia A, et al. Prospective study on the role of glucose metabolism in breast cancer occurrence. Int J Cancer 2012; 130: 921-9. http://dx.doi.org/10.1002/ijc.26071

Maccio A, Madeddu C. Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. ScientificWorldJournal 2011; 11: 2020-36. http://dx.doi.org/10.1100/2011/806787

Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer--chemoprevention strategies with a focus on metformin. Breast 2011; 20 Suppl 3: S31-5. http://dx.doi.org/10.1016/S0960-9776(11)70291-0

Probst-Hensch NM, Steiner JH, Schraml P, et al. IGFBP2 and IGFBP3 protein expressions in human breast cancer: association with hormonal factors and obesity. Clin Cancer Res 2010; 16: 1025-32. http://dx.doi.org/10.1158/1078-0432.CCR-09-0957

de Blaquiere GE, May FE, Westley BR. Increased expression of both insulin receptor substrates 1 and 2 confers increased sensitivity to IGF-1 stimulated cell migration. Endocr Relat Cancer 2009; 16: 635-47. http://dx.doi.org/10.1677/ERC-08-0216

Lanzino M, Morelli C, Garofalo C, et al. Interaction between estrogen receptor alpha and insulin/IGF signaling in breast cancer. Curr Cancer Drug Targets 2008; 8: 597-610. http://dx.doi.org/10.2174/156800908786241104

Pfeiler G, Treeck O, Wenzel G, et al. Influence of insulin resistance on adiponectin receptor expression in breast cancer. Maturitas 2009; 63: 253-6. http://dx.doi.org/10.1016/j.maturitas.2009.04.006

Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells. Diabetes Metab Res Rev 2009; 25: 41-9. http://dx.doi.org/10.1002/dmrr.912

Bulun SE, Chen D, Moy I, Brooks DC, Zhao H. Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab 2012; 23: 83-9. http://dx.doi.org/10.1016/j.tem.2011.10.003

Kyvernitakis I, Knoll D, Struck M, Hars O, Bauer T, Hadji P. Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole. J Cancer Res Clin Oncol 2014; 140: 159-66. http://dx.doi.org/10.1007/s00432-013-1557-3

Simpson ER, Brown KA. Obesity and breast cancer: role of inflammation and aromatase. J Mol Endocrinol 2013; 51: T51-9. http://dx.doi.org/10.1530/JME-13-0217

Howe LR, Subbaramaiah K, Hudis CA, Dannenberg AJ. Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer. Clin Cancer Res 2013; 19: 6074-83. http://dx.doi.org/10.1158/1078-0432.CCR-12-2603

Vona-Davis L, Rose DP. The obesity-inflammation-eicosanoid axis in breast cancer. J Mammary Gland Biol Neoplasia 2013; 18: 291-307. http://dx.doi.org/10.1007/s10911-013-9299-z

Pfeiler G, Konigsberg R, Hadji P, et al. Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer. Br J Cancer 2013; 109: 1522-7. http://dx.doi.org/10.1038/bjc.2013.499

Artac M, Bozcuk H, Kiyici A, Eren OO, Boruban MC, Ozdogan M. Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Breast Cancer 2013; 20: 174-80. http://dx.doi.org/10.1007/s12282-011-0322-1

Brown KA, Hunger NI, Docanto M, Simpson ER. Metformin inhibits aromatase expression in human breast adipose stromal cells via stimulation of AMP-activated protein kinase. Breast Cancer Res Treat 2010; 123: 591-6. http://dx.doi.org/10.1007/s10549-010-0834-y

Perrier S, Caldefie-Chezet F, Vasson MP. IL-1 family in breast cancer: potential interplay with leptin and other adipocytokines. FEBS Lett 2009; 583: 259-65. http://dx.doi.org/10.1016/j.febslet.2008.12.030

Soliman NA, Zineldeen DH, El-Khadrawy OH. Effect of NUCKS-1 overexpression on cytokine profiling in obese women with breast cancer. Asian Pac J Cancer Prev 2014; 15: 837-45. http://dx.doi.org/10.7314/APJCP.2014.15.2.837

Simpson ER, Brown KA. Minireview: Obesity and breast cancer: a tale of inflammation and dysregulated metabolism. Mol Endocrinol 2013; 27: 715-25. http://dx.doi.org/10.1210/me.2013-1011

Crujeiras AB, Diaz-Lagares A, Carreira MC, Amil M, Casanueva FF. Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer. Free Radic Res 2013; 47: 243-56. http://dx.doi.org/10.3109/10715762.2013.772604

Subbaramaiah K, Howe LR, Bhardwaj P, et al. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila) 2011; 4: 329-46. http://dx.doi.org/10.1158/1940-6207.CAPR-10-0381

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2015-01-29

How to Cite

Nehad M. Ayoub, & Amal Kaddoumi. (2015). Obesity and Breast Cancer: Molecular and Epidemiological Evidence. Journal of Cancer Research Updates, 4(1),  30–42. https://doi.org/10.6000/1929-2279.2015.04.01.3

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