Keywords: obesity, breast cancer, lipotoxicity, adiponectins


Background. Obesity, a global health burden and one of the most deleterious diseases have substantially increased prevalence attributable to changing lifestyle of modern times. Persuasive evidence indicates obesity as an independent prognostic factor for developing malignancy in the form of breast cancer particularly in post-menopausal women.

Objective. This review aims to focus in comprehensive manner on the biochemical, hormonal and immunological pathways governing the obesity linked breast cancer so that potential treatments may be improvised consequently to provide a cure to this menace, threatening the lives of many.

Methods. Literature review of published materials that provide examination of recent or current literature on problem of obesity.

Results. Increased body fatness, mainly visceral adiposity may account for predisposing an obese individual to the risk of encountering cancer although the mechanisms for such cancers may vary depending upon the organ affected. Metabolic and biochemical alterations influencing obesity related carcinogenesis, consisting of heightened oxidative stress and bodily inflammation levels with the concomitant rise in pro-inflammatory cytokines are discussed. Pertinent references about elevated levels of serum insulin, insulin-like growth factor, sex steroids and the imbalance in adipokines (adiponectin and leptin) are included as well.

Conclusions. Persuasive evidence indicates obesity as an independent prognostic factor for developing malignancy in the form of breast cancer particularly in post-menopausal women. Generation of novel and effective therapeutic interventions for combating the ailment along with positive lifestyle modifications may be improvised consequently to provide a cure to this menace, threatening the lives of many.

Author Biography


Assistant Professor

Department of Physiology

University of Calcutta


World Health Organization, Special Programme for Research, Training in Tropical Diseases, World Health Organization. Department of Control of Ne­glected Tropical Diseases, World Health Organization. Epidemic, Pandemic Alert. Dengue: guidelines for diagnosis, treatment, prevention and control. World Health Organization; 2009.

Peter T, Kuo Hadlay L, Conn Eugene A, DeFe­lice. Health & Obesity. Lippincott-Raven Publishers; 1983: 2.

Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. The lancet oncology. 2002 Sep 1;3(9):565-74.

Josefson D. Obesity fuels cancer epidemic. British Medical Journal, 2001: 322: 945.

McCann J. Obesity, cancer links prompt new recommendations. Journal of the National Cancer Institute. 2001 Jun 20;93(12):901-2.

World Health Organization. Obesity: pre­venting and managing the global epidemic. World Health Organization; 2000.

James PT. Obesity: the worldwide epidemic. Clinics in dermatology. 2004 Jul 1;22(4):276-80.

Manson JE, Willett WC, Stampfer MJ, Colditz GA, Hunter DJ, Hankinson SE, et al. Body weight and mortality among women. New England Journal of Medicine, 1995:333:677–85.

IARC. Weight Control and Physical Activity. IARCPress, Lyon, 2002.

Ceschi M, Gutzwiller F, Moch H, Eichholzer M, Probst-Hensch NM. Epidemiology and pathophy­siology of obesity as a cause of cancer. Swiss medical weekly. 2007 Jan 27;137(3/4):50.

McPherson K, Steel MC, Dixon MJ. Breast cancer-epidemiology, risk factors, and genetics. British Medical Journal, 2000. 21:1-5.

Pischon T, Nӧthlings, Boeing H. Symposium on ‘Diet and cancer’ Obesity and cancer. Proceedings of the Nutrition Society, 2008:67:128-145.

Rossen L, Rossen E. Obesity 101. Springer Publishing Company; 2011 Sep 19.

Berrington de Gonzalez A, Hartge P, Cer­han JR, Flint AJ, Hannan L, MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson WL. Body-mass index and mortality among 1.46 million white adults. New England Journal of Medicine. 2010 Dec 2;363(23):2211-9.

Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed me­chanisms. Nature Reviews Cancer. 2004 Aug; 4(8):579.

Van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiology and Prevention Bio­markers. 2009 Sep 15:1055-9965.

International Agency for Research on Cancer. IARC handbooks of cancer prevention. The Agency; 2002.

World Cancer Research Fund, American In­stitute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global per­spective. Amer Inst for Cancer Research; 2007.

Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. New England Journal of Medicine. 2003 Apr 24;348(17):1625-38.

Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. Jama. 2010 Jan 20;303(3):235-41.

Drew JE. Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin. Proceedings of the Nutrition Society. 2012 Feb;71(1):175-80.

Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocrine reviews. 2012 Aug 1;33(4):547-94.

Gallagher EJ, LeRoith D. Minireview: IGF, insulin, and cancer. Endocrinology. 2011 May 3;152(7):2546-51.

Hursting SD, Berger NA. Energy balance, host-related factors, and cancer progression. Journal of Clinical Oncology. 2010 Sep 10;28(26):4058.

Harvey AE, Lashinger LM, Hursting SD. The growing challenge of obesity and cancer: an inflammatory issue. Annals of the New York Academy of Sciences. 2011 Jul 1;1229(1):45-52.

Chen J. Multiple signal pathways in obesity-associated cancer. Obesity reviews. 2011 Dec;12(12): 1063-70.

Ferlay J, Autier P, Boniol M, Heanue M, Co­lombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of oncology. 2007 Feb 7;18(3):581-92.

Vera-Ramirez L, Ramirez-Tortosa MC, San­chez-Rovira P, Ramirez-Tortosa CL, Granados-Prin­cipal S, Lorente JA, Quiles JL. Impact of diet on breast cancer risk: a review of experimental and obser­vational studies. Critical reviews in food science and nutrition. 2013 Jan 1;53(1):49-75.

Hunter DJ, Willett WC. Epidemiology Review, 1993;15:110–132.

Ballard-Barbash R, Swanson CA. Body weight: estimation of risk for breast and endometrial can­cers. The American journal of clinical nutrition. 1996 Mar 1;63(3):437S-41S.

Trentham-Dietz A, Newcomb PA, Storer BE, Longnecker MP, Baron J, Greenberg ER, Willett WC. Body size and risk of breast cancer. American journal of epidemiology. 1997 Jun 1;145(11):1011-9.

Galanis DJ, Kolonel LN, Lee J, Le Marchand L. Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States. Cancer Causes & Control. 1998 Mar 1;9(2):217-24.

Stoll BA. Breast cancer and the western diet: role of fatty acids and antioxidant vitamins. European Journal of Cancer. 1998 Nov 1;34(12):1852-6.

Bayley JP, Devilee P. Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? Current opinion in genetics & development. 2010 Jun 30;20(3):324-9.

Bayley JP, Devilee P. The Warburg effect in 2012. Current opinion in oncology. 2012 Jan 1;24(1): 62-7.

Amadou A, Hainaut P, Romieu I. Role of obesity in the risk of breast cancer: lessons from anthropometry. Journal of oncology. 2013;19.

Brown KA, Simpson ER. Obesity and Breast Cancer. Briefs in Cancer Research. Springer, 2014.

Rana S, Blowers EC, Natarajan A. Small mole­cule adenosine 5′-monophosphate activated protein kinase (AMPK) modulators and human diseases. Journal of medicinal chemistry. 2014 Aug 28; 58(1):2 9.

Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proceedings of the Nutrition Society. 2001 Feb;60(1):91-106.

Stoll BA. Breast cancer and the western diet: role of fatty acids and antioxidant vitamins. European Journal of Cancer. 1998 Nov 1;34(12):1852-6.

Fürstenberger G, Senn HJ. Insulin-like growth factors and cancer. The lancet oncology. 2002 May 1;3(5):298-302.

Gupta K, Krishnaswamy G, Karnad A, Pei­ris AN. Insulin: a novel factor in carcinogenesis. The American journal of the medical sciences. 2002 Mar 1;323(3):140-5.

Renehan AG, Zwahlen M, Minder CT, O’Dwyer S, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. The Lancet. 2004 Apr 24;363(9418):1346-53.

Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin–IGF axis. Trends in Endocrinology & Metabolism. 2006 Oct 1;17(8):328-36.

Kaaks R, Lukanova A. Effects of weight control and physical activity in cancer prevention: role of endogenous hormone metabolism. Annals of the New York Academy of Sciences. 2002;963:268–81.

Harvie M, Renehan AG, Frystyk J, Flyvbjerg A, Mercer T, Malik R, Adams J, Cuzick J, Howell A. In­crease in serum total IGF-I and maintenance of free IGF-I following intentional weight loss in pre-me­nopausal women at increased risk of breast cancer. The Open Obesity Journal. 2010;2(2):63-70.

Renehan AG. Epidemiology of overweight/obesity and cancer risk. InPhysical activity, dietary calorie restriction, and cancer 2011 (pp. 5-23). Sprin­ger, New York, NY.

De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. Journal of obesity. 2013 Aug 29;2013.

Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, Vigneri R. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Archives of physiology and biochemistry. 2008 Jan 1;114(1):23-37.

Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Annals of the New York Academy of Sciences. 2012 Oct;1271(1):37-43.

Spindler SR. Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction. Mechanisms of ageing and deve­lopment. 2005 Sep 1;126(9):960-6.

Imayama I, Ulrich CM, Alfano CM, Wang C, Xiao L, Wener MH, Campbell KL, Duggan C, Foster-Schubert KE, Kong A, Mason CE. Effects of a caloric restriction weight loss diet and exercise on inflam­matory biomarkers in overweight/obese postme­nopausal women: a randomized controlled trial. Cancer research. 2012 May 1;72(9):2314-26.

Fine EJ, Segal-Isaacson CJ, Feinman RD, Herszkopf S, Romano MC, Tomuta N, Bontempo AF, Negassa A, Sparano JA. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition. 2012 Oct 1;28(10):1028-35.

Lagunova Z, Porojnicu AC, Grant WB, Bru­land Ø, Moan JE. Obesity and increased risk of cancer: Does decrease of serum 25-hydroxyvitamin D level with increasing body mass index explain some of the association? Molecular nutrition & food research. 2010 Aug;54(8):1127-33.

Hursting SD, Lashinger LM, Wheatley KW, Rogers CJ, Colbert LH, Nunez NP, Perkins SN. Re­ducing the weight of cancer: mechanistic targets for breaking the obesity–carcinogenesis link. Best practice & research Clinical endocrinology & meta_bolism. 2008 Aug 1;22(4):659-69.

Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. The lancet oncology. 2001 Mar 1;2(3):133-40.

Weiss LK, Burkman RT, Cushing-Haugen KL, Voigt LF, Simon MS, Daling JR, Norman SA, Bernstein L, Ursin G, Marchbanks PA, Strom BL. Hormone repla­cement therapy regimens and breast cancer risk1. Obstetrics & Gynecology. 2002 Dec 1;100(6):1148-58.

Van Leeuwen FE, Rookus MA. Breast cancer and hormone-replacement therapy: the million women study. Lancet, 2003; 362: 1330.

Ritte R, Lukanova A, Tjønneland A, Olsen A, Overvad K, Mesrine S, Fagherazzi G, Dossus L, Teucher B, Steindorf K, Boeing H. Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: A cohort study. International journal of cancer. 2013 Jun 1;132(11):2619-29.

Chlebowski RT, Aiello E, McTiernan A. Weight Loss in Breast Cancer Patient Management. Journal of Clinical Oncology, 2002;20:1128-43.

Han W, Kim SW, Park IA, Kang D, Kim SW, Youn YK, Oh SK, Choe KJ, Noh DY. Young age: an independent risk factor for disease-free survival in women with operable breast cancer. BMC cancer. 2004 Dec;4(1):82.

Renehan AG, Roberts DL, Dive C. Obesity and cancer: pathophysiological and biological mecha­nisms. Archives of physiology and biochemistry. 2008 Jan 1;114(1):71-83.

Travis RC, Key TJ. Oestrogen exposure and breast cancer risk. Breast Cancer Research. 2003 Oct;5(5):239.

Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PH, Biessy C, Dossus L, Lukanova A, Bingham S, Khaw KT, Allen NE. Postmenopausal serum androgens, oestro­gens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocrine-related cancer. 2005 Dec 1;12(4):1071-82.

Key TJ, Vogel VG. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Breast Diseases. 2004;15(1):33-33.

Rinaldi S, Key TJ, Peeters PH, Lahmann PH, Lukanova A, Dossus L, Biessy C, Vineis P, Sacerdote C, Berrino F, Panico S. Anthropometric measures, endo­genous sex steroids and breast cancer risk in post­menopausal women: a study within the EPIC cohort. International Journal of Cancer. 2006 Jun 1;118(11): 2832-9.

Potischman N, Swanson CA, Siiteri P, Hoo­ver RN. Reversal of relation between body mass and endogenous estrogen concentrations with meno­pausal status. Journal of National Cancer Institute, 1996;88:756–758.

Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ. Mammographic densities and breast cancer risk. Cancer Epidemiology and Prevention Biomar­kers. 1998 Dec 1;7(12):1133-44.

Hunt DA, Lane HM, Zygmont ME, Dervan PA, Hennigar RA. MRNA stability and overexpression of fatty acid synthase in human breast cancer cell lines. Anticancer research. 2007 Jan 1;27(1A):27-34.

Louie SM, Roberts LS, Nomura DK. Mecha­nisms linking obesity and cancer. Biochimica Et Biophysica Acta (bba)-Molecular And Cell Biology Of Lipids. 2013 Oct 31;1831(10):1499-508.

Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature Reviews Cancer. 2007 Oct;7(10):763.

Rajala MW, Scherer PE. Minireview: the adipocyte – at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003 Sep 1;144(9):3765-73.

Wang B, Trayhurn P. Acute and prolonged effects of TNF-α on the expression and secretion of inflammation-related adipokines by human adipo­cytes differentiated in culture. Pflügers Archiv. 2006 Jul 1;452(4):418-27.

Prins JB, Niesler CU, Winterford CM, Bright NA, Siddle K, O'rahilly S, Walker NI, Cameron DP. Tumor necrosis factor-α induces apoptosis of human adi­pose cells. Diabetes. 1997 Dec 1;46(12):1939-44.

Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α-and obesity-induced insulin resistance. Science. 1996 Feb 2;271(5249):665-70.

Stenlöf K, Wernstedt I, Fjällman T, Wallenius V, Wallenius K, Jansson JO. Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects. The Journal of Clinical Endocrinology & Metabolism. 2003 Sep 1;88(9):4379-83.

Liu M, Liu F. Transcriptional and post-trans­lational regulation of adiponectin. Biochemical Journal. 2010 Jan 1;425(1):41-52.

Watt MJ, Hevener A, Lancaster GI, Febbraio MA. Ciliary neurotrophic factor prevents acute lipid-induced insulin resistance by attenuating ceramide accumulation and phosphorylation of c-Jun N-ter­minal kinase in peripheral tissues. Endocrinology. 2006 May 1;147(5):2077-85.

Aljada A, Mohanty P, Ghanim H, Abdo T, Tripathy D, Chaudhuri A, Dandona P. Increase in intranuclear nuclear factor κB and decrease in inhibitor κB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. The American journal of clinical nutrition. 2004 Apr 1;79(4):682-90.

Solinas G, Karin M. JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction. The FASEB Journal. 2010 Aug;24(8):2596-611.

Nakamura T, Furuhashi M, Li P, Cao H, Tunc­man G, Sonenberg N, Gorgun CZ, Hotamisligil GS. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell. 2010 Feb 5;140(3):338-48.

Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science. 2010 Jan 15;327(5963):296-300.

Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid–induced insulin resistance. The Journal of clinical investigation. 2006 Nov 1;116(11):3015-25.

Song MJ, Kim KH, Yoon JM, Kim JB. Activation of Toll-like receptor 4 is associated with insulin re­sistance in adipocytes. Biochemical and biophysical research communications. 2006 Aug 4;346(3):739-45.

Boura-Halfon S, Zick Y. Phosphorylation of IRS proteins, insulin action, and insulin resistance. American Journal of Physiology-Endocrinology and Metabolism. 2009 Apr;296(4):E581-91.

Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. The Journal of Clinical Endocrinology & Metabolism. 2004 Jun 1;89(6):2548-56.

Friedman JM, Halaas JL. Leptin and the regu­lation of body weight in mammals. Nature. 1998 Oct;395(6704):763.

Vona-Davis L, Rose DP. Adipokines as endo­crine, paracrine, and autocrine factors in breast can­cer risk and progression. Endocrine-related can­cer. 2007 Jun 1;14(2):189-206.

Flier JS. What’s in a name? In search of lep­tin’s physiologic role. The Journal of Clinical Endo-crinology & Metabolism. 1998 May 1;83(5):1407-13.

Rosenbaum MI, Nicolson MA, Hirsch JU, Heymsfield SB, Gallagher DY, Chu FL, Leibel RL. Effects of gender, body composition, and menopause on plasma concentrations of leptin. The Journal of Cli­nical Endocrinology & Metabolism. 1996 Sep 1;81(9):3424-7.

Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Rangana­than S, Kern PA. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature medicine. 1995 Nov;1(11):1155.

Lönnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nature medicine. 1995 Sep;1(9):950.

Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H, Zhao L. Leptin induces functional activation of cyclooxy­ge­nase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer science. 2009 Mar;100(3):389-95.

Jaffe T, Schwartz B. Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal-transduction pathways. International Journal of Cancer. 2008 Dec 1;123(11): 2543-56.

Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, Noguchi S. Association of serum adiponectin levels with breast cancer risk. Clinical cancer research. 2003 Nov 15;9(15):5699-704.

Toi M, Taniguchi T, Ueno T, Asano M, Funa­ta N, Sekiguchi K, Iwanari H, Tominaga T. Significance of circulating hepatocyte growth factor level as a prognostic indicator in primary breast cancer. Clinical cancer research. 1998 Mar 1;4(3):659-64.

Sheen-Chen SM, Liu YW, Eng HL, Chou FF. Serum levels of hepatocyte growth factor in patients with breast cancer. Cancer Epidemiology and Pre­vention Biomarkers. 2005 Mar 1;14(3):715-7.

Taniguchi T, Toi M, Inada K, Imazawa T, Yamamoto Y, Tominaga T. Serum concentrations of hepatocyte growth factor in breast cancer patients. Clinical Cancer Research, 1995;1:1031–1034.

Kaplan W, Wirtz V, Mantel A, Béatrice PS. Priority Medicines for Europe and the World Update 2013 report. Methodology. 2013 May 29;2(7).

Last Medical Review. Breast Cancer. Ame­rican Cancer Society, 2014;1-127.

DeCensi A, Puntoni M, Goodwin P, Cazza­niga M, Gennari A, Bonanni B, Gandini S. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer prevention research. 2010 Oct 12:1940-6207.

Goodwin PJ, Ligibel JA, Stambolic V. Metformin in breast cancer: time for action. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009 Jul 10;27(20):3271.

Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. Journal of clinical oncology. 2009 Jul 10; 27(20):3297.

Shinde N, Shinde KJ, Khatri SM, Hande D. A comparative study of yoga and aerobic exercises in obesity and its effect on pulmonary function. J Diabetes Metab. 2013;4(257):2.

Sarvottam K, Yadav RK. Obesity-related inflammation & cardiovascular disease: Efficacy of a yoga-based lifestyle intervention. The Indian journal of medical research. 2014 Jun;139(6):822.

Stewart ST, Cutler DM, Rosen AB. Forecasting the effects of obesity and smoking on US life expec­tancy. New England Journal of Medicine. 2009 Dec 3;361(23):2252-60.

How to Cite
Roy, A., Basu, S., & Bandyopadhyay, A. (2019). OBESITY: A CAUSATIVE RISK FACTOR OF BREAST CANCER. International Journal of Medicine and Medical Research, 4(2), 50-58. https://doi.org/10.11603/ijmmr.2413-6077.2018.2.9410