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Obesity-associated Breast Cancer: Analysis of risk factors

Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 960)

Abstract

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women. While higher breast cancer risk with hormone replacement therapy is particularly evident among lean women, in postmenopausal women who are not taking exogenous hormones, general obesity is a significant predictor for breast cancer. Moreover, increased plasma cholesterol leads to accelerated tumor formation and exacerbates their aggressiveness. In contrast to postmenopausal women, premenopausal women with high BMI are inversely associated with breast cancer risk. Nevertheless, life-style of women for breast cancer risk is regulated by avoiding the overweight and a high-fat diet. Estrogen-plus-progestin hormone therapy users for more than 5 years have elevated risks of both invasive ductal and lobular breast cancer. Additionally, these cases are more commonly node-positive and have a higher cancer-related mortality. Collectively, in this chapter, the impacts of obesity-related estrogen, cholesterol, saturated fatty acid, leptin and adiponectin concentrations, aromatase activity, leptin and insulin resistance on breast cancer patients are evaluated. Obesity-related prognostic factors of breast cancer also are discussed at molecular basis.

Keywords

Breast cancer Obesity Fatty acid Postmenopausal breast cancer Premenopausal breast cancer Estrogen Leptin Adiponectin Aromatase Insulin resistance Mammalian target of rapamycin (mTOR) Insulin-like growth factor (IGF) Human epidermal growth factor receptor 2 (HER2) Estrogen receptor (ER) Progesteron receptor (PR) Cyclin D1 Liver X receptor (LXR) Oxysterol 27-hydroxycholesterol (27HC) Sex hormone-binding globulin (SHBG) Estrone Hypoxia Hyperinsulinemia Aryl hydrocarbon receptor (AHR) Breast cancer recurrence Cancer-associated adipocytes (CAAs) Leptin resistance 
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References

  1. Alikhani, N., R.D. Ferguson, R. Novosyadlyy, E.J. Gallagher, E.J. Scheinman, S. Yakar, and D. LeRoith. 2013. Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic mouse model. Oncogene 32: 961–967. doi: 10.1038/onc.2012.113.PubMedCrossRefGoogle Scholar
  2. Anderson, G.L., M. Limacher, A.R. Assaf, T. Bassford, S.A.A. Beresford, H. Black, D. Bonds, R. Brunner, R. Brzyski, B. Caan, R. Chlebowski, D. Curb, M. Gass, J. Hays, G. Heiss, S. Hendrix, B.V. Howard, J. Hsia, A. Hubbell, R. Jackson, K.C. Johnson, H. Judd, J.M. Kotchen, L. Kuller, A.Z. LaCroix, D. Lane, R.D. Langer, N. Lasser, C.E. Lewis, J. Manson, K. Margolis, J. Ockene, M.J. O’Sullivan, L. Phillips, R.L. Prentice, C. Ritenbaugh, J. Robbins, J.E. Rossouw, G. Sarto, M.L. Stefanick, L. Van Horn, J. Wactawski-Wende, R. Wallace, S. Wassertheil-Smoller, and Women’s Health Initiative Steering Committee. 2004. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association 291: 1701–1712. doi: 10.1001/jama.291.14.1701.PubMedCrossRefGoogle Scholar
  3. Badache, A., and N.E. Hynes. 2001. Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. Cancer Research 61: 383–391.PubMedGoogle Scholar
  4. Bagga, D., S. Capone, H.J. Wang, D. Heber, M. Lill, L. Chap, and J.A. Glaspy. 1997. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer. Journal of the National Cancer Institute 89: 1123–1131.PubMedCrossRefGoogle Scholar
  5. Bagga, D., K.H. Anders, H.-J. Wang, and J.A. Glaspy. 2002. Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer. Nutrition and Cancer 42: 180–185. doi: 10.1207/S15327914NC422_5.PubMedCrossRefGoogle Scholar
  6. Barb, D., K. Pazaitou-Panayiotou, and C.S. Mantzoros. 2006. Adiponectin: A link between obesity and cancer. Expert Opinion on Investigational Drugs 15: 917–931. doi: 10.1517/13543784.15.8.917.PubMedCrossRefGoogle Scholar
  7. Barhoover, M.A., J.M. Hall, W.F. Greenlee, and R.S. Thomas. 2010. Aryl hydrocarbon receptor regulates cell cycle progression in human breast cancer cells via a functional interaction with cyclin-dependent kinase 4. Molecular Pharmacology 77: 195–201. doi: 10.1124/mol.109.059675.PubMedCrossRefGoogle Scholar
  8. Bartella, V., S. Cascio, E. Fiorio, A. Auriemma, A. Russo, and E. Surmacz. 2008. Insulin-dependent leptin expression in breast cancer cells. Cancer Research 68: 4919–4927. doi: 10.1158/0008-5472.CAN-08-0642.PubMedCrossRefGoogle Scholar
  9. Benn, M., A. Tybjærg-Hansen, G.D. Smith, and B.G. Nordestgaard. 2016. High body mass index and cancer risk—A Mendelian randomisation study. European Journal of Epidemiology 31: 879–892. doi: 10.1007/s10654-016-0147-5.PubMedCrossRefGoogle Scholar
  10. Benoy, I., R. Salgado, C. Colpaert, R. Weytjens, P.B. Vermeulen, and L.Y. Dirix. 2002. Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. Clinical Breast Cancer 2: 311–315.PubMedCrossRefGoogle Scholar
  11. Biglia, N., E. Peano, P. Sgandurra, G. Moggio, S. Pecchio, F. Maggiorotto, and P. Sismondi. 2013. Body mass index (BMI) and breast cancer: Impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women. Gynecological Endocrinology 29: 263–267. doi: 10.3109/09513590.2012.736559.PubMedCrossRefGoogle Scholar
  12. Bjørbaek, C., S. Uotani, B. da Silva, and J.S. Flier. 1997. Divergent signaling capacities of the long and short isoforms of the leptin receptor. The Journal of Biological Chemistry 272: 32686–32695.PubMedCrossRefGoogle Scholar
  13. Bjørbaek, C., J.K. Elmquist, J.D. Frantz, S.E. Shoelson, and J.S. Flier. 1998. Identification of SOCS-3 as a potential mediator of central leptin resistance. Molecular Cell 1: 619–625.PubMedCrossRefGoogle Scholar
  14. Bjørbaek, C., K. El-Haschimi, J.D. Frantz, and J.S. Flier. 1999. The role of SOCS-3 in leptin signaling and leptin resistance. The Journal of Biological Chemistry 274: 30059–30065.PubMedCrossRefGoogle Scholar
  15. Blancafort, A., A. Giró-Perafita, G. Oliveras, S. Palomeras, C. Turrado, Ò. Campuzano, D. Carrión-Salip, A. Massaguer, R. Brugada, M. Palafox, J. Gómez-Miragaya, E. González-Suárez, and T. Puig. 2015. Dual fatty acid synthase and HER2 signaling blockade shows marked antitumor activity against breast cancer models resistant to anti-HER2 drugs. PLoS One 10: e0131241. doi: 10.1371/journal.pone.0131241.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bolton, J.L., and G.R.J. Thatcher. 2008. Potential mechanisms of estrogen quinone carcinogenesis. Chemical Research in Toxicology 21: 93–101. doi: 10.1021/tx700191p.PubMedCrossRefGoogle Scholar
  17. Boonyaratanakornkit, V., and P. Pateetin. 2015. The role of ovarian sex steroids in metabolic homeostasis, obesity, and postmenopausal breast cancer: Molecular mechanisms and therapeutic implications. BioMed Research International 2015: 140196. doi: 10.1155/2015/140196.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bowers, L.W., D.A. Cavazos, I.X.F. Maximo, A.J. Brenner, S.D. Hursting, and L.A. deGraffenried. 2013. Obesity enhances nongenomic estrogen receptor crosstalk with the PI3K/Akt and MAPK pathways to promote in vitro measures of breast cancer progression. Breast Cancer Research: BCR 15: R59. doi: 10.1186/bcr3453.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bowers, L.W., A.J. Brenner, S.D. Hursting, R.R. Tekmal, and L.A. deGraffenried. 2015. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production. Breast Cancer Research and Treatment 149: 49–57. doi: 10.1007/s10549-014-3223-0.PubMedCrossRefGoogle Scholar
  20. Boyd, N.F., and V. McGuire. 1990. Evidence of association between plasma high-density lipoprotein cholesterol and risk factors for breast cancer. Journal of the National Cancer Institute 82: 460–468.PubMedCrossRefGoogle Scholar
  21. Brodeur, M.R., L. Brissette, L. Falstrault, V. Luangrath, and R. Moreau. 2008. Scavenger receptor of class B expressed by osteoblastic cells are implicated in the uptake of cholesteryl ester and estradiol from LDL and HDL3. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research 23: 326–337. doi: 10.1359/jbmr.071022.CrossRefGoogle Scholar
  22. Brodie, A., Q. Lu, and J. Nakamura. 1997. Aromatase in the normal breast and breast cancer. The Journal of Steroid Biochemistry and Molecular Biology 61: 281–286.PubMedCrossRefGoogle Scholar
  23. Calder, P.C. 2012. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Molecular Nutrition & Food Research 56: 1073–1080. doi: 10.1002/mnfr.201100710.CrossRefGoogle Scholar
  24. Calle, E.E., H.S. Feigelson, J.S. Hildebrand, L.R. Teras, M.J. Thun, and C. Rodriguez. 2009. Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype. Cancer 115: 936–945. doi: 10.1002/cncr.24101.PubMedCrossRefGoogle Scholar
  25. Camoriano, J.K., C.L. Loprinzi, J.N. Ingle, T.M. Therneau, J.E. Krook, and M.H. Veeder. 1990. Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 8: 1327–1334. doi: 10.1200/jco.1990.8.8.1327.CrossRefGoogle Scholar
  26. Campbell, K.L., K.E. Foster-Schubert, C.M. Alfano, C.-C. Wang, C.-Y. Wang, C.R. Duggan, C. Mason, I. Imayama, A. Kong, L. Xiao, C.E. Bain, G.L. Blackburn, F.Z. Stanczyk, and A. McTiernan. 2012. Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal women: Randomized controlled trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 30: 2314–2326. doi: 10.1200/JCO.2011.37.9792.CrossRefGoogle Scholar
  27. Carroll, P.A., L. Healy, J. Lysaght, T. Boyle, J.V. Reynolds, M.J. Kennedy, G. Pidgeon, and E.M. Connolly. 2011. Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer. Molecular Carcinogenesis 50: 643–651. doi: 10.1002/mc.20764.PubMedCrossRefGoogle Scholar
  28. Catalano, S., S. Marsico, C. Giordano, L. Mauro, P. Rizza, M.L. Panno, and S. Andò. 2003. Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. The Journal of Biological Chemistry 278: 28668–28676. doi: 10.1074/jbc.M301695200.PubMedCrossRefGoogle Scholar
  29. Catalano, S., L. Mauro, S. Marsico, C. Giordano, P. Rizza, V. Rago, D. Montanaro, M. Maggiolini, M.L. Panno, and S. Andó. 2004. Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells. The Journal of Biological Chemistry 279: 19908–19915. doi: 10.1074/jbc.M313191200.PubMedCrossRefGoogle Scholar
  30. Catalano, S., L. Mauro, D. Bonofiglio, M. Pellegrino, H. Qi, P. Rizza, D. Vizza, G. Bossi, and S. Andò. 2011. In vivo and in vitro evidence that PPARγ ligands are antagonists of leptin signaling in breast cancer. The American Journal of Pathology 179: 1030–1040. doi: 10.1016/j.ajpath.2011.04.026.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Cavalieri, E., D. Chakravarti, J. Guttenplan, E. Hart, J. Ingle, R. Jankowiak, P. Muti, E. Rogan, J. Russo, R. Santen, and T. Sutter. 2006. Catechol estrogen quinones as initiators of breast and other human cancers: Implications for biomarkers of susceptibility and cancer prevention. Biochimica et Biophysica Acta 1766: 63–78. doi: 10.1016/j.bbcan.2006.03.001.PubMedGoogle Scholar
  32. Chan, D.S.M., A.R. Vieira, D. Aune, E.V. Bandera, D.C. Greenwood, A. McTiernan, D. Navarro Rosenblatt, I. Thune, R. Vieira, and T. Norat. 2014. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Annals of Oncology 25: 1901–1914. doi: 10.1093/annonc/mdu042.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Chang, C.-C., M.-J. Wu, J.-Y. Yang, I.G. Camarillo, and C.-J. Chang. 2015. Leptin-STAT3-G9a signaling promotes obesity-mediated breast cancer progression. Cancer Research 75: 2375–2386. doi: 10.1158/0008-5472.CAN-14-3076.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Chavey, C., F. Bibeau, S. Gourgou-Bourgade, S. Burlinchon, F. Boissière, D. Laune, S. Roques, and G. Lazennec. 2007. Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Research: BCR 9: R15. doi: 10.1186/bcr1648.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Chen, X., and Y. Wang. 2011. Adiponectin and breast cancer. Medical Oncology (Northwood, London, England) 28: 1288–1295. doi: 10.1007/s12032-010-9617-x.CrossRefGoogle Scholar
  36. Chen, D.-C., Y.-F. Chung, Y.-T. Yeh, H.-C. Chaung, F.-C. Kuo, O.-Y. Fu, H.-Y. Chen, M.-F. Hou, and S.-S.F. Yuan. 2006. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Letters 237: 109–114. doi: 10.1016/j.canlet.2005.05.047.PubMedCrossRefGoogle Scholar
  37. Chen, D., H. Zhao, J.S. Coon, M. Ono, E.K. Pearson, and S.E. Bulun. 2012. Weight gain increases human aromatase expression in mammary gland. Molecular and Cellular Endocrinology 355: 114–120. doi: 10.1016/j.mce.2012.01.027.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Chlebowski, R.T., G.L. Anderson, M. Gass, D.S. Lane, A.K. Aragaki, L.H. Kuller, J.E. Manson, M.L. Stefanick, J. Ockene, G.E. Sarto, K.C. Johnson, J. Wactawski-Wende, P.M. Ravdin, R. Schenken, S.L. Hendrix, A. Rajkovic, T.E. Rohan, S. Yasmeen, R.L. Prentice, and WHI Investigators. 2010. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. Journal of the American Medical Association 304: 1684–1692. doi: 10.1001/jama.2010.1500.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Chlebowski, R.T., T.E. Rohan, J.E. Manson, A.K. Aragaki, A. Kaunitz, M.L. Stefanick, M.S. Simon, K.C. Johnson, J. Wactawski-Wende, M.J. O’Sullivan, L.L. Adams-Campbell, R. Nassir, L.S. Lessin, and R.L. Prentice. 2015. Breast cancer after use of estrogen plus progestin and estrogen alone: Analyses of data from 2 Women’s Health Initiative randomized clinical trials. JAMA Oncology 1: 296–305. doi: 10.1001/jamaoncol.2015.0494.PubMedCrossRefGoogle Scholar
  40. Cleary, M.P., and M.E. Grossmann. 2009. Minireview: Obesity and breast cancer: The estrogen connection. Endocrinology 150: 2537–2542. doi: 10.1210/en.2009-0070.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Cleary, M.P., J.P. Grande, S.C. Juneja, and N.J. Maihle. 2004a. Diet-induced obesity and mammary tumor development in MMTV-neu female mice. Nutrition and Cancer 50: 174–180. doi: 10.1207/s15327914nc5002_7.PubMedCrossRefGoogle Scholar
  42. Cleary, M.P., S.C. Juneja, F.C. Phillips, X. Hu, J.P. Grande, and N.J. Maihle. 2004b. Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. Experimental Biology and Medicine (Maywood, NJ) 229: 182–193.CrossRefGoogle Scholar
  43. Cooke, P.S., P.A. Heine, J.A. Taylor, and D.B. Lubahn. 2001. The role of estrogen and estrogen receptor-alpha in male adipose tissue. Molecular and Cellular Endocrinology 178: 147–154.PubMedCrossRefGoogle Scholar
  44. D’Esposito, V., F. Passaretti, A. Hammarstedt, D. Liguoro, D. Terracciano, G. Molea, L. Canta, C. Miele, U. Smith, F. Beguinot, and P. Formisano. 2012. Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro. Diabetologia 55: 2811–2822. doi: 10.1007/s00125-012-2629-7.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Dalamaga, M., K.N. Diakopoulos, and C.S. Mantzoros. 2012. The role of adiponectin in cancer: A review of current evidence. Endocrine Reviews 33: 547–594. doi: 10.1210/er.2011-1015.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Davis, S.R., C. Castelo-Branco, P. Chedraui, M.A. Lumsden, R.E. Nappi, D. Shah, P. Villaseca, and Writing Group of the International Menopause Society for World Menopause Day 2012. 2012. Understanding weight gain at menopause. Climacteric: The Journal of the International Menopause Society 15: 419–429. doi: 10.3109/13697137.2012.707385.CrossRefGoogle Scholar
  47. DeBerardinis, R.J., J.J. Lum, G. Hatzivassiliou, and C.B. Thompson. 2008. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism 7: 11–20. doi: 10.1016/j.cmet.2007.10.002.PubMedCrossRefGoogle Scholar
  48. Del Giudice, M.E., I.G. Fantus, S. Ezzat, G. McKeown-Eyssen, D. Page, and P.J. Goodwin. 1998. Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Research and Treatment 47: 111–120.PubMedCrossRefGoogle Scholar
  49. Delort, L., T. Jardé, V. Dubois, M.-P. Vasson, and F. Caldefie-Chézet. 2012. New insights into anticarcinogenic properties of adiponectin: A potential therapeutic approach in breast cancer? Vitamins and Hormones 90: 397–417. doi: 10.1016/B978-0-12-398313-8.00015-4.PubMedCrossRefGoogle Scholar
  50. Delort, L., A. Rossary, M.-C. Farges, M.-P. Vasson, and F. Caldefie-Chézet. 2015. Leptin, adipocytes and breast cancer: Focus on inflammation and anti-tumor immunity. Life Sciences 140: 37–48. doi: 10.1016/j.lfs.2015.04.012.PubMedCrossRefGoogle Scholar
  51. Demark-Wahnefried, W., K.L. Campbell, and S.C. Hayes. 2012. Weight management and its role in breast cancer rehabilitation. Cancer 118: 2277–2287. doi: 10.1002/cncr.27466.PubMedCrossRefGoogle Scholar
  52. DeMichele, A., R. Gray, M. Horn, J. Chen, R. Aplenc, W.P. Vaughan, and M.S. Tallman. 2009. Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer. Cancer Research 69: 4184–4191. doi: 10.1158/0008-5472.CAN-08-2989.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Denison, M.S., A.A. Soshilov, G. He, D.E. DeGroot, and B. Zhao. 2011. Exactly the same but different: Promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicological Sciences 124: 1–22. doi: 10.1093/toxsci/kfr218.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Deroo, B.J., and K.S. Korach. 2006. Estrogen receptors and human disease. The Journal of Clinical Investigation 116: 561–570. doi: 10.1172/JCI27987.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Dethlefsen, C., G. Højfeldt, and P. Hojman. 2013. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Research and Treatment 138: 657–664. doi: 10.1007/s10549-013-2488-z.PubMedCrossRefGoogle Scholar
  56. Dignam, J.J., K. Wieand, K.A. Johnson, B. Fisher, L. Xu, and E.P. Mamounas. 2003. Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. Journal of the National Cancer Institute 95: 1467–1476.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Diorio, C., J. Lemieux, L. Provencher, J.-C. Hogue, and E. Vachon. 2012. Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels. Breast Cancer Research and Treatment 136: 573–579. doi: 10.1007/s10549-012-2278-z.PubMedCrossRefGoogle Scholar
  58. Dirat, B., L. Bochet, M. Dabek, D. Daviaud, S. Dauvillier, B. Majed, Y.Y. Wang, A. Meulle, B. Salles, S. Le Gonidec, I. Garrido, G. Escourrou, P. Valet, and C. Muller. 2011. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Research 71: 2455–2465. doi: 10.1158/0008-5472.CAN-10-3323.PubMedCrossRefGoogle Scholar
  59. Duan, C., M. Li, and L. Rui. 2004. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. The Journal of Biological Chemistry 279: 43684–43691. doi: 10.1074/jbc.M408495200.PubMedCrossRefGoogle Scholar
  60. Duggan, C., M.L. Irwin, L. Xiao, K.D. Henderson, A.W. Smith, R.N. Baumgartner, K.B. Baumgartner, L. Bernstein, R. Ballard-Barbash, and A. McTiernan. 2011. Associations of insulin resistance and adiponectin with mortality in women with breast cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 29: 32–39. doi: 10.1200/JCO.2009.26.4473.CrossRefGoogle Scholar
  61. Elmquist, J.K., C. Bjørbaek, R.S. Ahima, J.S. Flier, and C.B. Saper. 1998. Distributions of leptin receptor mRNA isoforms in the rat brain. The Journal of Comparative Neurology 395: 535–547.PubMedCrossRefGoogle Scholar
  62. Elstner, E., C. Müller, K. Koshizuka, E.A. Williamson, D. Park, H. Asou, P. Shintaku, J.W. Said, D. Heber, and H.P. Koeffler. 1998. Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proceedings of the National Academy of Sciences of the United States of America 95: 8806–8811.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Esteban, J.M., Z. Warsi, M. Haniu, P. Hall, J.E. Shively, and S. Chen. 1992. Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation. The American Journal of Pathology 140: 337–343.PubMedPubMedCentralGoogle Scholar
  64. Ewertz, M., M.-B. Jensen, K.Á. Gunnarsdóttir, I. Højris, E.H. Jakobsen, D. Nielsen, L.E. Stenbygaard, U.B. Tange, and S. Cold. 2011. Effect of obesity on prognosis after early-stage breast cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 29: 25–31. doi: 10.1200/JCO.2010.29.7614.CrossRefGoogle Scholar
  65. Ewertz, M., K.P. Gray, M.M. Regan, B. Ejlertsen, K.N. Price, B. Thürlimann, H. Bonnefoi, J.F. Forbes, R.J. Paridaens, M. Rabaglio, R.D. Gelber, M. Colleoni, I. Láng, I.E. Smith, A.S. Coates, A. Goldhirsch, and H.T. Mouridsen. 2012. Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 30: 3967–3975. doi: 10.1200/JCO.2011.40.8666.CrossRefGoogle Scholar
  66. Fedele, P., L. Orlando, P. Schiavone, A. Quaranta, A.M. Lapolla, M. De Pasquale, A. Ardizzone, E. Bria, I. Sperduti, N. Calvani, A. Marino, C. Caliolo, E. Mazzoni, and S. Cinieri. 2014. BMI variation increases recurrence risk in women with early-stage breast cancer. Future Oncology (London, England) 10: 2459–2468. doi: 10.2217/fon.14.180.CrossRefGoogle Scholar
  67. Fiorio, E., A. Mercanti, M. Terrasi, R. Micciolo, A. Remo, A. Auriemma, A. Molino, V. Parolin, B. Di Stefano, F. Bonetti, A. Giordano, G.L. Cetto, and E. Surmacz. 2008. Leptin/HER2 crosstalk in breast cancer: In vitro study and preliminary in vivo analysis. BMC Cancer 8: 305. doi: 10.1186/1471-2407-8-305.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Frederich, R.C., A. Hamann, S. Anderson, B. Löllmann, B.B. Lowell, and J.S. Flier. 1995. Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nature Medicine 1: 1311–1314.PubMedCrossRefGoogle Scholar
  69. Frystyk, J., C. Skjaerbaek, E. Vestbo, S. Fisker, and H. Orskov. 1999. Circulating levels of free insulin-like growth factors in obese subjects: The impact of type 2 diabetes. Diabetes/Metabolism Research and Reviews 15: 314–322.PubMedCrossRefGoogle Scholar
  70. Fu, X., J.G. Menke, Y. Chen, G. Zhou, K.L. MacNaul, S.D. Wright, C.P. Sparrow, and E.G. Lund. 2001. 27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. The Journal of Biological Chemistry 276: 38378–38387. doi: 10.1074/jbc.M105805200.PubMedCrossRefGoogle Scholar
  71. Garofalo, C., D. Sisci, and E. Surmacz. 2004. Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells. Clinical Cancer Research 10: 6466–6475. doi: 10.1158/1078-0432.CCR-04-0203.PubMedCrossRefGoogle Scholar
  72. Geisler, J., B. Haynes, D. Ekse, M. Dowsett, and P.E. Lønning. 2007. Total body aromatization in postmenopausal breast cancer patients is strongly correlated to plasma leptin levels. The Journal of Steroid Biochemistry and Molecular Biology 104: 27–34. doi: 10.1016/j.jsbmb.2006.09.040.PubMedCrossRefGoogle Scholar
  73. Gelaleti, G.B., B.V. Jardim, C. Leonel, M.G. Moschetta, and D.A. Zuccari. 2012. Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias. Veterinary Immunology and Immunopathology 146: 106–112. doi: 10.1016/j.vetimm.2012.02.005.PubMedCrossRefGoogle Scholar
  74. Ghilardi, N., and R.C. Skoda. 1997. The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. Molecular Endocrinology (Baltimore, Md.) 11: 393–399. doi: 10.1210/mend.11.4.9907.CrossRefGoogle Scholar
  75. Giordano, C., D. Vizza, S. Panza, I. Barone, D. Bonofiglio, M. Lanzino, D. Sisci, F. De Amicis, S.A.W. Fuqua, S. Catalano, and S. Andò. 2013. Leptin increases HER2 protein levels through a STAT3-mediated up-regulation of Hsp90 in breast cancer cells. Molecular Oncology 7: 379–391. doi: 10.1016/j.molonc.2012.11.002.PubMedCrossRefGoogle Scholar
  76. Giró-Perafita, A., S. Palomeras, D.H. Lum, A. Blancafort, G. Viñas, G. Oliveras, F. Pérez-Bueno, A. Sarrats, A.L. Welm, and T. Puig. 2016. Preclinical evaluation of fatty acid synthase and EGFR inhibition in triple-negative breast cancer. Clinical Cancer Research 22: 4687–4697. doi: 10.1158/1078-0432.CCR-15-3133.PubMedCrossRefGoogle Scholar
  77. Gong, H., P. Guo, Y. Zhai, J. Zhou, H. Uppal, M.J. Jarzynka, W.-C. Song, S.-Y. Cheng, and W. Xie. 2007. Estrogen deprivation and inhibition of breast cancer growth in vivo through activation of the orphan nuclear receptor liver X receptor. Molecular Endocrinology (Baltimore, Md.) 21: 1781–1790. doi: 10.1210/me.2007-0187.CrossRefGoogle Scholar
  78. Goodwin, P.J. 2013. Obesity and endocrine therapy: Host factors and breast cancer outcome. Breast (Edinburgh, Scotland) 22(Suppl 2): S44–S47. doi: 10.1016/j.breast.2013.07.008.CrossRefGoogle Scholar
  79. Goodwin, P.J., M. Ennis, K.I. Pritchard, M.E. Trudeau, J. Koo, Y. Madarnas, W. Hartwick, B. Hoffman, and N. Hood. 2002. Fasting insulin and outcome in early-stage breast cancer: Results of a prospective cohort study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 20: 42–51. doi: 10.1200/jco.2002.20.1.42.CrossRefGoogle Scholar
  80. Goodwin, P.J., M. Ennis, K.I. Pritchard, M.E. Trudeau, J. Koo, S.K. Taylor, and N. Hood. 2012. Insulin- and obesity-related variables in early-stage breast cancer: Correlations and time course of prognostic associations. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 30: 164–171. doi: 10.1200/JCO.2011.36.2723.CrossRefGoogle Scholar
  81. Grewal, T., I. de Diego, M.F. Kirchhoff, F. Tebar, J. Heeren, F. Rinninger, and C. Enrich. 2003. High density lipoprotein-induced signaling of the MAPK pathway involves scavenger receptor type BI-mediated activation of Ras. The Journal of Biological Chemistry 278: 16478–16481. doi: 10.1074/jbc.C300085200.PubMedCrossRefGoogle Scholar
  82. Grossmann, M.E., A. Ray, K.J. Nkhata, D.A. Malakhov, O.P. Rogozina, S. Dogan, and M.P. Cleary. 2010. Obesity and breast cancer: Status of leptin and adiponectin in pathological processes. Cancer Metastasis Reviews 29: 641–653. doi: 10.1007/s10555-010-9252-1.PubMedCrossRefGoogle Scholar
  83. Guaita-Esteruelas, S., A. Bosquet, P. Saavedra, J. Gumà, J. Girona, E.W.-F. Lam, K. Amillano, J. Borràs, and L. Masana. 2016. Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins. Molecular Carcinogenesis 56(1): 208–217. doi: 10.1002/mc.22485.PubMedCrossRefGoogle Scholar
  84. Gunter, M.J., D.R. Hoover, H. Yu, S. Wassertheil-Smoller, T.E. Rohan, J.E. Manson, J. Li, G.Y.F. Ho, X. Xue, G.L. Anderson, R.C. Kaplan, T.G. Harris, B.V. Howard, J. Wylie-Rosett, R.D. Burk, and H.D. Strickler. 2009. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. Journal of the National Cancer Institute 101: 48–60. doi: 10.1093/jnci/djn415.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Guo, S., and R.R. Gonzalez-Perez. 2011. Notch, IL-1 and leptin crosstalk outcome (NILCO) is critical for leptin-induced proliferation, migration and VEGF/VEGFR-2 expression in breast cancer. PLoS One 6: e21467. doi: 10.1371/journal.pone.0021467.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Guo, S., M. Liu, and R.R. Gonzalez-Perez. 2011. Role of Notch and its oncogenic signaling crosstalk in breast cancer. Biochimica et Biophysica Acta 1815: 197–213. doi: 10.1016/j.bbcan.2010.12.002.PubMedGoogle Scholar
  87. Guo, S., M. Liu, G. Wang, M. Torroella-Kouri, and R.R. Gonzalez-Perez. 2012. Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochimica et Biophysica Acta 1825: 207–222. doi: 10.1016/j.bbcan.2012.01.002.PubMedPubMedCentralGoogle Scholar
  88. Gupta, P.B., D. Proia, O. Cingoz, J. Weremowicz, S.P. Naber, R.A. Weinberg, and C. Kuperwasser. 2007. Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Research 67: 2062–2071. doi: 10.1158/0008-5472.CAN-06-3895.PubMedCrossRefGoogle Scholar
  89. Haakinson, D.J., S.G. Leeds, A.C. Dueck, R.J. Gray, N. Wasif, C.-C.H. Stucky, D.W. Northfelt, H.A. Apsey, and B. Pockaj. 2012. The impact of obesity on breast cancer: A retrospective review. Annals of Surgical Oncology 19: 3012–3018. doi: 10.1245/s10434-012-2320-8.PubMedCrossRefGoogle Scholar
  90. Hancke, K., D. Grubeck, N. Hauser, R. Kreienberg, and J.M. Weiss. 2010. Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients. Breast Cancer Research and Treatment 119: 367–367. doi: 10.1007/s10549-009-0577-9.PubMedCrossRefGoogle Scholar
  91. Hardy, S., G.G. St-Onge, E. Joly, Y. Langelier, and M. Prentki. 2005. Oleate promotes the proliferation of breast cancer cells via the G protein-coupled receptor GPR40. The Journal of Biological Chemistry 280: 13285–13291. doi: 10.1074/jbc.M410922200.PubMedCrossRefGoogle Scholar
  92. Hawsawi, Y., R. El-Gendy, C. Twelves, V. Speirs, and J. Beattie. 2013. Insulin-like growth factor—Oestradiol crosstalk and mammary gland tumourigenesis. Biochimica et Biophysica Acta 1836: 345–353. doi: 10.1016/j.bbcan.2013.10.005.PubMedGoogle Scholar
  93. Heim, M.H. 1999. The Jak-STAT pathway: Cytokine signalling from the receptor to the nucleus. Journal of Receptor and Signal Transduction Research 19: 75–120. doi: 10.3109/10799899909036638.PubMedCrossRefGoogle Scholar
  94. Heldring, N., A. Pike, S. Andersson, J. Matthews, G. Cheng, J. Hartman, M. Tujague, A. Ström, E. Treuter, M. Warner, and J.-A. Gustafsson. 2007. Estrogen receptors: How do they signal and what are their targets. Physiological Reviews 87: 905–931. doi: 10.1152/physrev.00026.2006.PubMedCrossRefGoogle Scholar
  95. Henderson, B.E., and H.S. Feigelson. 2000. Hormonal carcinogenesis. Carcinogenesis 21: 427–433.PubMedCrossRefGoogle Scholar
  96. Hernandez, A.V., M. Guarnizo, Y. Miranda, V. Pasupuleti, A. Deshpande, S. Paico, H. Lenti, S. Ganoza, L. Montalvo, P. Thota, and H. Lazaro. 2014. Association between insulin resistance and breast carcinoma: A systematic review and meta-analysis. PLoS One 9: e99317. doi: 10.1371/journal.pone.0099317.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Hoeflich, A., and V.C. Russo. 2015. Physiology and pathophysiology of IGFBP-1 and IGFBP-2—Consensus and dissent on metabolic control and malignant potential. Best Practice & Research. Clinical Endocrinology & Metabolism 29: 685–700. doi: 10.1016/j.beem.2015.07.002.CrossRefGoogle Scholar
  98. Honma, S., K. Shimodaira, Y. Shimizu, N. Tsuchiya, H. Saito, T. Yanaihara, and T. Okai. 2002. The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells. Endocrine Journal 49: 371–377.PubMedCrossRefGoogle Scholar
  99. Huang, Z., S.E. Hankinson, G.A. Colditz, M.J. Stampfer, D.J. Hunter, J.E. Manson, C.H. Hennekens, B. Rosner, F.E. Speizer, and W.C. Willett. 1997. Dual effects of weight and weight gain on breast cancer risk. Journal of the American Medical Association 278: 1407–1411.PubMedCrossRefGoogle Scholar
  100. Ishikawa, M., J. Kitayama, and H. Nagawa. 2004. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clinical Cancer Research 10: 4325–4331. doi: 10.1158/1078-0432.CCR-03-0749.PubMedCrossRefGoogle Scholar
  101. Iyengar, P., T.P. Combs, S.J. Shah, V. Gouon-Evans, J.W. Pollard, C. Albanese, L. Flanagan, M.P. Tenniswood, C. Guha, M.P. Lisanti, R.G. Pestell, and P.E. Scherer. 2003. Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 22: 6408–6423. doi: 10.1038/sj.onc.1206737.PubMedCrossRefGoogle Scholar
  102. Iyengar, N.M., C.A. Hudis, and A.J. Dannenberg. 2013. Obesity and inflammation: New insights into breast cancer development and progression. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Meeting 46–51. doi:10.1200/EdBook_AM.2013.33.46.Google Scholar
  103. Iyengar, N.M., X.K. Zhou, A. Gucalp, P.G. Morris, L.R. Howe, D.D. Giri, M. Morrow, H. Wang, M. Pollak, L.W. Jones, C.A. Hudis, and A.J. Dannenberg. 2016. Systemic correlates of white adipose tissue inflammation in early-stage breast cancer. Clinical Cancer Research 22: 2283–2289. doi: 10.1158/1078-0432.CCR-15-2239.PubMedCrossRefGoogle Scholar
  104. Jackson, J.G., M.F. White, and D. Yee. 1998. Insulin receptor substrate-1 is the predominant signaling molecule activated by insulin-like growth factor-I, insulin, and interleukin-4 in estrogen receptor-positive human breast cancer cells. The Journal of Biological Chemistry 273: 9994–10003.PubMedCrossRefGoogle Scholar
  105. Jardé, T., F. Caldefie-Chézet, M. Damez, F. Mishellany, F. Penault-Llorca, J. Guillot, and M.P. Vasson. 2008. Leptin and leptin receptor involvement in cancer development: A study on human primary breast carcinoma. Oncology Reports 19: 905–911.PubMedGoogle Scholar
  106. Kadowaki, T., and T. Yamauchi. 2005. Adiponectin and adiponectin receptors. Endocrine Reviews 26: 439–451. doi: 10.1210/er.2005-0005.PubMedCrossRefGoogle Scholar
  107. Kamel, M., S. Shouman, M. El-Merzebany, G. Kilic, T. Veenstra, M. Saeed, M. Wagih, C. Diaz-Arrastia, D. Patel, and S. Salama. 2012. Effect of tumour necrosis factor-alpha on estrogen metabolic pathways in breast cancer cells. Journal of Cancer 3: 310–321. doi: 10.7150/jca.4584.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Kamineni, A., M.L. Anderson, E. White, S.H. Taplin, P. Porter, R. Ballard-Barbash, K. Malone, and D.S.M. Buist. 2013. Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population. Cancer Causes & Control: CCC 24: 305–312. doi: 10.1007/s10552-012-0115-7.PubMedCrossRefGoogle Scholar
  109. Kang, J.-H., B.-Y. Yu, and D.-S. Youn. 2007. Relationship of serum adiponectin and resistin levels with breast cancer risk. Journal of Korean Medical Science 22: 117–121. doi: 10.3346/jkms.2007.22.1.117.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Karuna, R., A.G. Holleboom, M.M. Motazacker, J.A. Kuivenhoven, R. Frikke-Schmidt, A. Tybjaerg-Hansen, S. Georgopoulos, M. van Eck, T.J.C. van Berkel, A. von Eckardstein, and K.M. Rentsch. 2011. Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism. Atherosclerosis 214: 448–455. doi: 10.1016/j.atherosclerosis.2010.10.042.PubMedCrossRefGoogle Scholar
  111. Kaur, B., A. Jørgensen, and A.K. Duttaroy. 2009. Fatty acid uptake by breast cancer cells (MDA-MB-231): Effects of insulin, leptin, adiponectin, and TNFalpha. Prostaglandins, Leukotrienes, and Essential Fatty Acids 80: 93–99. doi: 10.1016/j.plefa.2009.01.002.PubMedCrossRefGoogle Scholar
  112. Khaidakov, M., S. Mitra, B.-Y. Kang, X. Wang, S. Kadlubar, G. Novelli, V. Raj, M. Winters, W.C. Carter, and J.L. Mehta. 2011. Oxidized LDL receptor 1 (OLR1) as a possible link between obesity, dyslipidemia and cancer. PLoS One 6: e20277. doi: 10.1371/journal.pone.0020277.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Khan, S., S. Shukla, S. Sinha, and S.M. Meeran. 2013. Role of adipokines and cytokines in obesity-associated breast cancer: Therapeutic targets. Cytokine & Growth Factor Reviews 24: 503–513. doi: 10.1016/j.cytogfr.2013.10.001.CrossRefGoogle Scholar
  114. Khandekar, M.J., P. Cohen, and B.M. Spiegelman. 2011. Molecular mechanisms of cancer development in obesity. Nature Reviews. Cancer 11: 886–895. doi: 10.1038/nrc3174.PubMedCrossRefGoogle Scholar
  115. Kim, H.-S., A.R. Ingermann, J. Tsubaki, S.M. Twigg, G.E. Walker, and Y. Oh. 2004. Insulin-like growth factor-binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7 human breast cancer cells. Cancer Research 64: 2229–2237.PubMedCrossRefGoogle Scholar
  116. Kim, J., Y.H. Lee, J.H.Y. Park, and M.-K. Sung. 2015. Estrogen deprivation and excess energy supply accelerate 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in C3H/HeN mice. Nutrition Research and Practice 9: 628–636. doi: 10.4162/nrp.2015.9.6.628.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Kinlaw, W.B., P.W. Baures, L.E. Lupien, W.L. Davis, and N.B. Kuemmerle. 2016. Fatty acids and breast cancer: Make them on site or have them delivered. Journal of Cellular Physiology 231: 2128–2141. doi: 10.1002/jcp.25332.PubMedCrossRefGoogle Scholar
  118. Korkaya, H., A. Paulson, F. Iovino, and M.S. Wicha. 2008. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27: 6120–6130. doi: 10.1038/onc.2008.207.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Körner, A., K. Pazaitou-Panayiotou, T. Kelesidis, I. Kelesidis, C.J. Williams, A. Kaprara, J. Bullen, A. Neuwirth, S. Tseleni, N. Mitsiades, W. Kiess, and C.S. Mantzoros. 2007. Total and high-molecular-weight adiponectin in breast cancer: In vitro and in vivo studies. The Journal of Clinical Endocrinology and Metabolism 92: 1041–1048. doi: 10.1210/jc.2006-1858.PubMedCrossRefGoogle Scholar
  120. Kroenke, C.H., W.Y. Chen, B. Rosner, and M.D. Holmes. 2005. Weight, weight gain, and survival after breast cancer diagnosis. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 23: 1370–1378. doi: 10.1200/JCO.2005.01.079.CrossRefGoogle Scholar
  121. Kumar-Sinha, C., K.W. Ignatoski, M.E. Lippman, S.P. Ethier, and A.M. Chinnaiyan. 2003. Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis. Cancer Research 63: 132–139.PubMedGoogle Scholar
  122. Kurtzman, S.H., K.H. Anderson, Y. Wang, L.J. Miller, M. Renna, M. Stankus, R.R. Lindquist, G. Barrows, and D.L. Kreutzer. 1999. Cytokines in human breast cancer: IL-1alpha and IL-1beta expression. Oncology Reports 6: 65–70.PubMedGoogle Scholar
  123. Lahmann, P.H., K. Hoffmann, N. Allen, C.H. van Gils, K.-T. Khaw, B. Tehard, F. Berrino, A. Tjønneland, J. Bigaard, A. Olsen, K. Overvad, F. Clavel-Chapelon, G. Nagel, H. Boeing, D. Trichopoulos, G. Economou, G. Bellos, D. Palli, R. Tumino, S. Panico, C. Sacerdote, V. Krogh, P.H.M. Peeters, H.B. Bueno-de-Mesquita, E. Lund, E. Ardanaz, P. Amiano, G. Pera, J.R. Quirós, C. Martínez, M.J. Tormo, E. Wirfält, G. Berglund, G. Hallmans, T.J. Key, G. Reeves, S. Bingham, T. Norat, C. Biessy, R. Kaaks, and E. Riboli. 2004. Body size and breast cancer risk: Findings from the European Prospective Investigation into Cancer And Nutrition (EPIC). International Journal of Cancer 111: 762–771. doi: 10.1002/ijc.20315.PubMedCrossRefGoogle Scholar
  124. Lashinger, L.M., L.M. Malone, M.J. McArthur, J.A. Goldberg, E.A. Daniels, A. Pavone, J.K. Colby, N.C. Smith, S.N. Perkins, S.M. Fischer, and S.D. Hursting. 2011. Genetic reduction of insulin-like growth factor-1 mimics the anticancer effects of calorie restriction on cyclooxygenase-2-driven pancreatic neoplasia. Cancer Prevention Research (Philadelphia, Pa.) 4: 1030–1040. doi: 10.1158/1940-6207.CAPR-11-0027.CrossRefGoogle Scholar
  125. Lazarus, R., D. Sparrow, and S. Weiss. 1998. Temporal relations between obesity and insulin: Longitudinal data from the Normative Aging Study. American Journal of Epidemiology 147: 173–179.PubMedCrossRefGoogle Scholar
  126. Lee, J.Y., J. Ye, Z. Gao, H.S. Youn, W.H. Lee, L. Zhao, N. Sizemore, and D.H. Hwang. 2003. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. The Journal of Biological Chemistry 278: 37041–37051. doi: 10.1074/jbc.M305213200.PubMedCrossRefGoogle Scholar
  127. Li, C.I., K.E. Malone, and J.R. Daling. 2006. Interactions between body mass index and hormone therapy and postmenopausal breast cancer risk (United States). Cancer Causes & Control: CCC 17: 695–703. doi: 10.1007/s10552-005-0001-7.PubMedCrossRefGoogle Scholar
  128. Li, Z., Y. Zhou, C. Carter-Su, M.G. Myers, and L. Rui. 2007. SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms. Molecular Endocrinology (Baltimore, Md.) 21: 2270–2281. doi: 10.1210/me.2007-0111.CrossRefGoogle Scholar
  129. Lin, M.T., C.Y. Juan, K.J. Chang, W.J. Chen, and M.L. Kuo. 2001. IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1. Carcinogenesis 22: 1947–1953.PubMedCrossRefGoogle Scholar
  130. Lindet, C., F. Révillion, V. Lhotellier, L. Hornez, J.-P. Peyrat, and J. Bonneterre. 2012. Relationships between progesterone receptor isoforms and the HER/ErbB receptors and ligands network in 299 primary breast cancers. The International Journal of Biological Markers 27: e111–e117. doi: 10.5301/JBM.2012.9198.PubMedCrossRefGoogle Scholar
  131. Liu, C., J. Wu, J. Zhu, C. Kuei, J. Yu, J. Shelton, S.W. Sutton, X. Li, S.J. Yun, T. Mirzadegan, C. Mazur, F. Kamme, and T.W. Lovenberg. 2009. Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. The Journal of Biological Chemistry 284: 2811–2822. doi: 10.1074/jbc.M806409200.PubMedCrossRefGoogle Scholar
  132. Llaverias, G., C. Danilo, I. Mercier, K. Daumer, F. Capozza, T.M. Williams, F. Sotgia, M.P. Lisanti, and P.G. Frank. 2011. Role of cholesterol in the development and progression of breast cancer. The American Journal of Pathology 178: 402–412. doi: 10.1016/j.ajpath.2010.11.005.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Lønning, P.E., B.P. Haynes, and M. Dowsett. 2014. Relationship of body mass index with aromatisation and plasma and tissue oestrogen levels in postmenopausal breast cancer patients treated with aromatase inhibitors. European Journal of Cancer (Oxford, England: 1990) 1990(50): 1055–1064. doi: 10.1016/j.ejca.2014.01.007.CrossRefGoogle Scholar
  134. Lovejoy, J.C. 2003. The menopause and obesity. Primary Care 30: 317–325.PubMedCrossRefGoogle Scholar
  135. Lukanova, A., E. Lundin, A. Zeleniuch-Jacquotte, P. Muti, A. Mure, S. Rinaldi, L. Dossus, A. Micheli, A. Arslan, P. Lenner, R.E. Shore, V. Krogh, K.L. Koenig, E. Riboli, F. Berrino, G. Hallmans, P. Stattin, P. Toniolo, and R. Kaaks. 2004. Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: A cross-sectional study in healthy women. European Journal of Endocrinology 150: 161–171.PubMedCrossRefGoogle Scholar
  136. Macciò, A., and C. Madeddu. 2011. Obesity, inflammation, and postmenopausal breast cancer: Therapeutic implications. ScientificWorldJournal 11: 2020–2036. doi: 10.1100/2011/806787.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Maddams, J., D. Brewster, A. Gavin, J. Steward, J. Elliott, M. Utley, and H. Møller. 2009. Cancer prevalence in the United Kingdom: Estimates for 2008. British Journal of Cancer 101: 541–547. doi: 10.1038/sj.bjc.6605148.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Madeddu, C., G. Gramignano, C. Floris, G. Murenu, G. Sollai, and A. Macciò. 2014. Role of inflammation and oxidative stress in post-menopausal oestrogen-dependent breast cancer. Journal of Cellular and Molecular Medicine 18: 2519–2529. doi: 10.1111/jcmm.12413.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Maffei, M., J. Halaas, E. Ravussin, R.E. Pratley, G.H. Lee, Y. Zhang, H. Fei, S. Kim, R. Lallone, and S. Ranganathan. 1995. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine 1: 1155–1161.PubMedCrossRefGoogle Scholar
  140. Magoffin, D.A., S.R. Weitsman, S.K. Aagarwal, and A.J. Jakimiuk. 1999. Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women. Ginekologia Polska 70: 1–7.PubMedGoogle Scholar
  141. Mantzoros, C., E. Petridou, N. Dessypris, C. Chavelas, M. Dalamaga, D.M. Alexe, Y. Papadiamantis, C. Markopoulos, E. Spanos, G. Chrousos, and D. Trichopoulos. 2004. Adiponectin and breast cancer risk. The Journal of Clinical Endocrinology and Metabolism 89: 1102–1107. doi: 10.1210/jc.2003-031804.PubMedCrossRefGoogle Scholar
  142. Mauro, L., M. Pellegrino, F. De Amicis, E. Ricchio, F. Giordano, P. Rizza, S. Catalano, D. Bonofiglio, D. Sisci, M.L. Panno, and S. Andò. 2014. Evidences that estrogen receptor α interferes with adiponectin effects on breast cancer cell growth. Cell Cycle (Georgetown, Texas) 13: 553–564. doi: 10.4161/cc.27455.CrossRefGoogle Scholar
  143. Mauro, L., M. Pellegrino, F. Giordano, E. Ricchio, P. Rizza, F. De Amicis, S. Catalano, D. Bonofiglio, M.L. Panno, and S. Andò. 2015. Estrogen receptor-α drives adiponectin effects on cyclin D1 expression in breast cancer cells. FASEB Journal 29: 2150–2160. doi: 10.1096/fj.14-262808.PubMedCrossRefGoogle Scholar
  144. McCusker, R.H., C. Camacho-Hubner, M.L. Bayne, M.A. Cascieri, and D.R. Clemmons. 1990. Insulin-like growth factor (IGF) binding to human fibroblast and glioblastoma cells: The modulating effect of cell released IGF binding proteins (IGFBPs). Journal of Cellular Physiology 144: 244–253. doi: 10.1002/jcp.1041440210.PubMedCrossRefGoogle Scholar
  145. McDonnell, D.P., C.-Y. Chang, and E.R. Nelson. 2014a. The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer. Climacteric: The Journal of the International Menopause Society 17(Suppl 2): 60–65. doi: 10.3109/13697137.2014.966949.CrossRefGoogle Scholar
  146. McDonnell, D.P., S. Park, M.T. Goulet, J. Jasper, S.E. Wardell, C.-Y. Chang, J.D. Norris, J.R. Guyton, and E.R. Nelson. 2014b. Obesity, cholesterol metabolism, and breast cancer pathogenesis. Cancer Research 74: 4976–4982. doi: 10.1158/0008-5472.CAN-14-1756.PubMedPubMedCentralCrossRefGoogle Scholar
  147. McTiernan, A., K.B. Rajan, S.S. Tworoger, M. Irwin, L. Bernstein, R. Baumgartner, F. Gilliland, F.Z. Stanczyk, Y. Yasui, and R. Ballard-Barbash. 2003. Adiposity and sex hormones in postmenopausal breast cancer survivors. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 21: 1961–1966. doi: 10.1200/JCO.2003.07.057.CrossRefGoogle Scholar
  148. McTiernan, A., L. Wu, C. Chen, R. Chlebowski, Y. Mossavar-Rahmani, F. Modugno, M.G. Perri, F.Z. Stanczyk, L. Van Horn, C.Y. Wang, and Women’s Health Initiative Investigators. 2006. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring, Md.) 14: 1662–1677. doi: 10.1038/oby.2006.191.CrossRefGoogle Scholar
  149. Merdad, A., S. Karim, H.-J. Schulten, M. Jayapal, A. Dallol, A. Buhmeida, F. Al-Thubaity, M.A. GariI, A.G.A. Chaudhary, A.M. Abuzenadah, and M.H. Al-Qahtani. 2015. Transcriptomics profiling study of breast cancer from Kingdom of Saudi Arabia revealed altered expression of Adiponectin and Fatty Acid Binding Protein4: Is lipid metabolism associated with breast cancer? BMC Genomics 16(Suppl 1): S11. doi: 10.1186/1471-2164-16-S1-S11.PubMedPubMedCentralCrossRefGoogle Scholar
  150. Miller, W.R., and J. O’Neill. 1987. The importance of local synthesis of estrogen within the breast. Steroids 50: 537–548.PubMedCrossRefGoogle Scholar
  151. Millikan, R.C., B. Newman, C.-K. Tse, P.G. Moorman, K. Conway, L.G. Dressler, L.V. Smith, M.H. Labbok, J. Geradts, J.T. Bensen, S. Jackson, S. Nyante, C. Livasy, L. Carey, H.S. Earp, and C.M. Perou. 2008. Epidemiology of basal-like breast cancer. Breast Cancer Research and Treatment 109: 123–139. doi: 10.1007/s10549-007-9632-6.PubMedCrossRefGoogle Scholar
  152. Minatoya, M., G. Kutomi, H. Shima, S. Asakura, S. Otokozawa, H. Ohnishi, H. Akasaka, T. Miura, M. Mori, and K. Hirata. 2014. Relation of serum adiponectin levels and obesity with breast cancer: A Japanese case-control study. Asian Pacific Journal of Cancer Prevention: APJCP 15: 8325–8330.PubMedCrossRefGoogle Scholar
  153. Minokoshi, Y., Y.-B. Kim, O.D. Peroni, L.G.D. Fryer, C. Müller, D. Carling, and B.B. Kahn. 2002. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415: 339–343. doi: 10.1038/415339a.PubMedCrossRefGoogle Scholar
  154. Miyoshi, Y., T. Funahashi, S. Kihara, T. Taguchi, Y. Tamaki, Y. Matsuzawa, and S. Noguchi. 2003. Association of serum adiponectin levels with breast cancer risk. Clinical Cancer Research 9: 5699–5704.PubMedGoogle Scholar
  155. Mohamed-Ali, V., S. Goodrick, A. Rawesh, D.R. Katz, J.M. Miles, J.S. Yudkin, S. Klein, and S.W. Coppack. 1997. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. The Journal of Clinical Endocrinology and Metabolism 82: 4196–4200. doi: 10.1210/jcem.82.12.4450.PubMedGoogle Scholar
  156. Monk, J.M., H.F. Turk, D.M. Liddle, A.A. De Boer, K.A. Power, D.W.L. Ma, and L.E. Robinson. 2014. n-3 polyunsaturated fatty acids and mechanisms to mitigate inflammatory paracrine signaling in obesity-associated breast cancer. Nutrients 6: 4760–4793. doi: 10.3390/nu6114760.PubMedPubMedCentralCrossRefGoogle Scholar
  157. Morad, V., A. Abrahamsson, and C. Dabrosin. 2014. Estradiol affects extracellular leptin:adiponectin ratio in human breast tissue in vivo. The Journal of Clinical Endocrinology and Metabolism 99: 3460–3467. doi: 10.1210/jc.2014-1129.PubMedCrossRefGoogle Scholar
  158. Morris, D.L., and L. Rui. 2009. Recent advances in understanding leptin signaling and leptin resistance. American Journal of Physiology. Endocrinology and Metabolism 297: E1247–E1259. doi: 10.1152/ajpendo.00274.2009.PubMedPubMedCentralCrossRefGoogle Scholar
  159. Morris, P.G., C.A. Hudis, D. Giri, M. Morrow, D.J. Falcone, X.K. Zhou, B. Du, E. Brogi, C.B. Crawford, L. Kopelovich, K. Subbaramaiah, and A.J. Dannenberg. 2011. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prevention Research (Philadelphia, Pa.) 4: 1021–1029. doi: 10.1158/1940-6207.CAPR-11-0110.CrossRefGoogle Scholar
  160. Mueller, S.O., and K.S. Korach. 2001. Estrogen receptors and endocrine diseases: Lessons from estrogen receptor knockout mice. Current Opinion in Pharmacology 1: 613–619.PubMedCrossRefGoogle Scholar
  161. Nakayama, S., Y. Miyoshi, H. Ishihara, and S. Noguchi. 2008. Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis. Breast Cancer Research and Treatment 112: 405–410. doi: 10.1007/s10549-007-9874-3.PubMedCrossRefGoogle Scholar
  162. Nam, S., S. Park, H.S. Park, S. Kim, J.Y. Kim, and S.I. Kim. 2016. Association between insulin resistance and luminal B subtype breast cancer in postmenopausal women. Medicine (Baltimore) 95: e2825. doi: 10.1097/MD.0000000000002825.CrossRefGoogle Scholar
  163. Navarro-Tito, N., A. Soto-Guzman, L. Castro-Sanchez, R. Martinez-Orozco, and E.P. Salazar. 2010. Oleic acid promotes migration on MDA-MB-231 breast cancer cells through an arachidonic acid-dependent pathway. The International Journal of Biochemistry & Cell Biology 42: 306–317. doi: 10.1016/j.biocel.2009.11.010.CrossRefGoogle Scholar
  164. Nechuta, S., W.Y. Chen, H. Cai, E.M. Poole, M.L. Kwan, S.W. Flatt, R.E. Patterson, J.P. Pierce, B.J. Caan, and X. Ou Shu. 2016. A pooled analysis of post-diagnosis lifestyle factors in association with late estrogen-receptor-positive breast cancer prognosis. International Journal of Cancer 138: 2088–2097. doi: 10.1002/ijc.29940.PubMedCrossRefGoogle Scholar
  165. Nelson, E.R., S.E. Wardell, J.S. Jasper, S. Park, S. Suchindran, M.K. Howe, N.J. Carver, R.V. Pillai, P.M. Sullivan, V. Sondhi, M. Umetani, J. Geradts, and D.P. McDonnell. 2013. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science 342: 1094–1098. doi: 10.1126/science.1241908.PubMedPubMedCentralCrossRefGoogle Scholar
  166. Oh, S.W., C.-Y. Park, E.S. Lee, Y.S. Yoon, E.S. Lee, S.S. Park, Y. Kim, N.J. Sung, Y.H. Yun, K.S. Lee, H.S. Kang, Y. Kwon, and J. Ro. 2011. Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: A cohort study. Breast Cancer Research: BCR 13: R34. doi: 10.1186/bcr2856.PubMedPubMedCentralCrossRefGoogle Scholar
  167. Ota, D.M., L.A. Jones, G.L. Jackson, P.M. Jackson, K. Kemp, and D. Bauman. 1986. Obesity, non-protein-bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients. Cancer 57: 558–562.PubMedCrossRefGoogle Scholar
  168. Ozbay, T., and R. Nahta. 2008. A novel unidirectional cross-talk from the insulin-like growth factor-I receptor to leptin receptor in human breast cancer cells. Molecular Cancer Research: MCR 6: 1052–1058. doi: 10.1158/1541-7786.MCR-07-2126.PubMedPubMedCentralCrossRefGoogle Scholar
  169. Pantschenko, A.G., I. Pushkar, K.H. Anderson, Y. Wang, L.J. Miller, S.H. Kurtzman, G. Barrows, and D.L. Kreutzer. 2003. The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression. International Journal of Oncology 23: 269–284.PubMedGoogle Scholar
  170. Papanikolaou, V., N. Stefanou, S. Dubos, I. Papathanasiou, M. Palianopoulou, V. Valiakou, and A. Tsezou. 2015. Synergy of leptin/STAT3 with HER2 receptor induces tamoxifen resistance in breast cancer cells through regulation of apoptosis-related genes. Cellular Oncology (Dordrecht) 38: 155–164. doi: 10.1007/s13402-014-0213-5.CrossRefGoogle Scholar
  171. Park, S., C.-Y. Chang, R. Safi, X. Liu, R. Baldi, J.S. Jasper, G.R. Anderson, T. Liu, J.C. Rathmell, M.W. Dewhirst, K.C. Wood, J.W. Locasale, and D.P. McDonnell. 2016. ERRα-regulated lactate metabolism contributes to resistance to targeted therapies in breast cancer. Cell Reports 15: 323–335. doi: 10.1016/j.celrep.2016.03.026.PubMedPubMedCentralCrossRefGoogle Scholar
  172. Pathak, D.R., and A.S. Whittemore. 1992. Combined effects of body size, parity, and menstrual events on breast cancer incidence in seven countries. American Journal of Epidemiology 135: 153–168.PubMedCrossRefGoogle Scholar
  173. Peacock, S.L., E. White, J.R. Daling, L.F. Voigt, and K.E. Malone. 1999. Relation between obesity and breast cancer in young women. American Journal of Epidemiology 149: 339–346.PubMedCrossRefGoogle Scholar
  174. Peck, B., Z.T. Schug, Q. Zhang, B. Dankworth, D.T. Jones, E. Smethurst, R. Patel, S. Mason, M. Jiang, R. Saunders, M. Howell, R. Mitter, B. Spencer-Dene, G. Stamp, L. McGarry, D. James, E. Shanks, E.O. Aboagye, S.E. Critchlow, H.Y. Leung, A.L. Harris, M.J.O. Wakelam, E. Gottlieb, and A. Schulze. 2016. Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer & Metabolism 4: 6. doi: 10.1186/s40170-016-0146-8.CrossRefGoogle Scholar
  175. Peiró, G., E. Adrover, L. Sánchez-Tejada, E. Lerma, M. Planelles, J. Sánchez-Payá, F.I. Aranda, D. Giner, and F.J. Gutiérrez-Aviñó. 2011. Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 24: 201–208. doi: 10.1038/modpathol.2010.191.CrossRefGoogle Scholar
  176. Pfeiler, G.H., C. Buechler, M. Neumeier, A. Schäffler, G. Schmitz, O. Ortmann, and O. Treeck. 2008. Adiponectin effects on human breast cancer cells are dependent on 17-beta estradiol. Oncology Reports 19: 787–793.PubMedGoogle Scholar
  177. Pfeiler, G., R. Königsberg, P. Hadji, F. Fitzal, M. Maroske, G. Dressel-Ban, J. Zellinger, R. Exner, M. Seifert, C. Singer, M. Gnant, and P. Dubsky. 2013. Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer. British Journal of Cancer 109: 1522–1527. doi: 10.1038/bjc.2013.499.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Pfeilschifter, J., R. Köditz, M. Pfohl, and H. Schatz. 2002. Changes in proinflammatory cytokine activity after menopause. Endocrine Reviews 23: 90–119. doi: 10.1210/edrv.23.1.0456.PubMedCrossRefGoogle Scholar
  179. Phoenix, K.N., F. Vumbaca, M.M. Fox, R. Evans, and K.P. Claffey. 2010. Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy. Breast Cancer Research and Treatment 123: 333–344. doi: 10.1007/s10549-009-0647-z.PubMedCrossRefGoogle Scholar
  180. Picon-Ruiz, M., C. Pan, K. Drews-Elger, K. Jang, A.H. Besser, D. Zhao, C. Morata-Tarifa, M. Kim, T.A. Ince, D.J. Azzam, S.A. Wander, B. Wang, B. Ergonul, R.H. Datar, R.J. Cote, G.A. Howard, D. El-Ashry, P. Torné-Poyatos, J.A. Marchal, and J.M. Slingerland. 2016. Interactions between adipocytes and breast cancer cells stimulate cytokine production and drive Src/Sox2/miR-302b-mediated malignant progression. Cancer Research 76: 491–504. doi: 10.1158/0008-5472.CAN-15-0927.PubMedCrossRefGoogle Scholar
  181. Pierobon, M., and C.L. Frankenfeld. 2013. Obesity as a risk factor for triple-negative breast cancers: A systematic review and meta-analysis. Breast Cancer Research and Treatment 137: 307–314. doi: 10.1007/s10549-012-2339-3.PubMedCrossRefGoogle Scholar
  182. Playdon, M.C., M.B. Bracken, T.B. Sanft, J.A. Ligibel, M. Harrigan, and M.L. Irwin. 2015. Weight gain after breast cancer diagnosis and all-cause mortality: Systematic review and meta-analysis. Journal of the National Cancer Institute 107: djv275. doi: 10.1093/jnci/djv275.PubMedPubMedCentralCrossRefGoogle Scholar
  183. Pollak, M.N. 1998. Endocrine effects of IGF-I on normal and transformed breast epithelial cells: Potential relevance to strategies for breast cancer treatment and prevention. Breast Cancer Research and Treatment 47: 209–217.PubMedCrossRefGoogle Scholar
  184. Pollak, M. 2008. Insulin and insulin-like growth factor signalling in neoplasia. Nature Reviews. Cancer 8: 915–928. doi: 10.1038/nrc2536.PubMedCrossRefGoogle Scholar
  185. Pollenz, R.S. 2002. The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation. Chemico-Biological Interactions 141: 41–61.PubMedCrossRefGoogle Scholar
  186. Porta, R., A. Blancafort, G. Casòliva, M. Casas, J. Dorca, M. Buxo, G. Viñas, G. Oliveras, and T. Puig. 2014. Fatty acid synthase expression is strongly related to menopause in early-stage breast cancer patients. Menopause (New York, N.Y.) 21: 188–191. doi: 10.1097/GME.0b013e31829d17dc.CrossRefGoogle Scholar
  187. Prosperi, J.R., and F.M. Robertson. 2006. Cyclooxygenase-2 directly regulates gene expression of P450 Cyp19 aromatase promoter regions pII, pI.3 and pI.7 and estradiol production in human breast tumor cells. Prostaglandins & Other Lipid Mediators 81: 55–70. doi: 10.1016/j.prostaglandins.2006.07.003.CrossRefGoogle Scholar
  188. Protani, M., M. Coory, and J.H. Martin. 2010. Effect of obesity on survival of women with breast cancer: Systematic review and meta-analysis. Breast Cancer Research and Treatment 123: 627–635. doi: 10.1007/s10549-010-0990-0.PubMedCrossRefGoogle Scholar
  189. Puig, T., A. Vázquez-Martín, J. Relat, J. Pétriz, J.A. Menéndez, R. Porta, G. Casals, P.F. Marrero, D. Haro, J. Brunet, and R. Colomer. 2008. Fatty acid metabolism in breast cancer cells: Differential inhibitory effects of epigallocatechin gallate (EGCG) and C75. Breast Cancer Research and Treatment 109: 471–479. doi: 10.1007/s10549-007-9678-5.PubMedCrossRefGoogle Scholar
  190. Purohit, A., D.Y. Wang, M.W. Ghilchik, and M.J. Reed. 1996. Regulation of aromatase and sulphatase in breast tumour cells. The Journal of Endocrinology 150(Suppl): S65–S71.PubMedGoogle Scholar
  191. Purohit, A., S.P. Newman, and M.J. Reed. 2002. The role of cytokines in regulating estrogen synthesis: Implications for the etiology of breast cancer. Breast Cancer Research: BCR 4: 65–69.PubMedPubMedCentralCrossRefGoogle Scholar
  192. Qian, Y., D. Shi, J. Qiu, F. Zhu, J. Qian, S. He, Y. Shu, Y. Yin, and X. Chen. 2015. ObRb downregulation increases breast cancer cell sensitivity to tamoxifen. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 36: 6813–6821. doi: 10.1007/s13277-015-3375-5.CrossRefGoogle Scholar
  193. Railo, M.J., K. von Smitten, and F. Pekonen. 1994. The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients. European Journal of Cancer (Oxford, England: 1990) 30A: 307–311.CrossRefGoogle Scholar
  194. Reed, M.J., L. Topping, N.G. Coldham, A. Purohit, M.W. Ghilchik, and V.H. James. 1993. Control of aromatase activity in breast cancer cells: The role of cytokines and growth factors. The Journal of Steroid Biochemistry and Molecular Biology 44: 589–596.PubMedCrossRefGoogle Scholar
  195. Renehan, A.G., J. Frystyk, and A. Flyvbjerg. 2006. Obesity and cancer risk: The role of the insulin-IGF axis. Trends in Endocrinology and Metabolism: TEM 17: 328–336. doi: 10.1016/j.tem.2006.08.006.PubMedCrossRefGoogle Scholar
  196. Renehan, A.G., M. Tyson, M. Egger, R.F. Heller, and M. Zwahlen. 2008. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet (London, England) 371: 569–578. doi: 10.1016/S0140-6736(08)60269-X.CrossRefGoogle Scholar
  197. Révillion, F., M. Charlier, V. Lhotellier, L. Hornez, S. Giard, M.-C. Baranzelli, J. Djiane, and J.-P. Peyrat. 2006. Messenger RNA expression of leptin and leptin receptors and their prognostic value in 322 human primary breast cancers. Clinical Cancer Research 12: 2088–2094. doi: 10.1158/1078-0432.CCR-05-1904.PubMedCrossRefGoogle Scholar
  198. Richards, J.A., T.A. Petrel, and R.W. Brueggemeier. 2002. Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells. The Journal of Steroid Biochemistry and Molecular Biology 80: 203–212.PubMedCrossRefGoogle Scholar
  199. Robinson, P.J., R.J. Bell, and S.R. Davis. 2014. Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer. Maturitas 79: 279–286. doi: 10.1016/j.maturitas.2014.07.004.PubMedCrossRefGoogle Scholar
  200. Rock, C.L., S.W. Flatt, G.A. Laughlin, E.B. Gold, C.A. Thomson, L. Natarajan, L.A. Jones, B.J. Caan, M.L. Stefanick, R.A. Hajek, W.K. Al-Delaimy, F.Z. Stanczyk, J.P. Pierce, and Women’s Healthy Eating and Living Study Group. 2008. Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer. Cancer Epidemiology, Biomarkers & Prevention 17: 614–620. doi: 10.1158/1055-9965.EPI-07-0761.CrossRefGoogle Scholar
  201. Rock, C.L., C. Doyle, W. Demark-Wahnefried, J. Meyerhardt, K.S. Courneya, A.L. Schwartz, E.V. Bandera, K.K. Hamilton, B. Grant, M. McCullough, T. Byers, and T. Gansler. 2012. Nutrition and physical activity guidelines for cancer survivors. CA: A Cancer Journal for Clinicians 62: 243–274. doi: 10.3322/caac.21142.Google Scholar
  202. Romero-Figueroa, M.S., J.J. Garduño-García, J. Duarte-Mote, G. Matute-González, A. Gómez-Villanueva, and J. De la Cruz-Vargas. 2013. Insulin and leptin levels in obese patients with and without breast cancer. Clinical Breast Cancer 13: 482–485. doi: 10.1016/j.clbc.2013.08.001.CrossRefGoogle Scholar
  203. Rose, D.P., and J.M. Connolly. 1999. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacology & Therapeutics 83: 217–244.CrossRefGoogle Scholar
  204. Rose, D.P., and L. Vona-Davis. 2014. Biochemical and molecular mechanisms for the association between obesity, chronic inflammation, and breast cancer. BioFactors (Oxford, England) 40: 1–12. doi: 10.1002/biof.1109.CrossRefGoogle Scholar
  205. Rossouw, J.E., G.L. Anderson, R.L. Prentice, A.Z. LaCroix, C. Kooperberg, M.L. Stefanick, R.D. Jackson, S.A.A. Beresford, B.V. Howard, K.C. Johnson, J.M. Kotchen, J. Ockene, and Writing Group for the Women’s Health Initiative Investigators. 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association 288: 321–333.PubMedCrossRefGoogle Scholar
  206. Salisbury, T.B., G.Z. Morris, J.K. Tomblin, A.R. Chaudhry, C.R. Cook, and N. Santanam. 2013. Aryl hydrocarbon receptor ligands inhibit IGF-II and adipokine stimulated breast cancer cell proliferation. ISRN Endocrinology 2013: 104850. doi: 10.1155/2013/104850.PubMedPubMedCentralCrossRefGoogle Scholar
  207. Samarajeewa, N.U., F. Yang, M.M. Docanto, M. Sakurai, K.M. McNamara, H. Sasano, S.B. Fox, E.R. Simpson, and K.A. Brown. 2013. HIF-1α stimulates aromatase expression driven by prostaglandin E2 in breast adipose stroma. Breast Cancer Research: BCR 15: R30. doi: 10.1186/bcr3410.PubMedPubMedCentralCrossRefGoogle Scholar
  208. Santen, R., E. Cavalieri, E. Rogan, J. Russo, J. Guttenplan, J. Ingle, and W. Yue. 2009. Estrogen mediation of breast tumor formation involves estrogen receptor-dependent, as well as independent, genotoxic effects. Annals of the New York Academy of Sciences 1155: 132–140. doi: 10.1111/j.1749-6632.2008.03685.x.PubMedCrossRefGoogle Scholar
  209. Sasano, H., and N. Harada. 1998. Intratumoral aromatase in human breast, endometrial, and ovarian malignancies. Endocrine Reviews 19: 593–607. doi: 10.1210/edrv.19.5.0342.PubMedGoogle Scholar
  210. Sasano, H., T. Suzuki, T. Nakata, and T. Moriya. 2006. New development in intracrinology of breast carcinoma. Breast Cancer (Tokyo, Japan) 13: 129–136.CrossRefGoogle Scholar
  211. Sasser, A.K., N.J. Sullivan, A.W. Studebaker, L.F. Hendey, A.E. Axel, and B.M. Hall. 2007. Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB Journal 21: 3763–3770. doi: 10.1096/fj.07-8832com.PubMedCrossRefGoogle Scholar
  212. Schapira, D.V., N.B. Kumar, and G.H. Lyman. 1991. Obesity, body fat distribution, and sex hormones in breast cancer patients. Cancer 67: 2215–2218.PubMedCrossRefGoogle Scholar
  213. Scott, M.M., J.L. Lachey, S.M. Sternson, C.E. Lee, C.F. Elias, J.M. Friedman, and J.K. Elmquist. 2009. Leptin targets in the mouse brain. The Journal of Comparative Neurology 514: 518–532. doi: 10.1002/cne.22025.PubMedPubMedCentralCrossRefGoogle Scholar
  214. Serna-Marquez, N., S. Villegas-Comonfort, O. Galindo-Hernandez, N. Navarro-Tito, A. Millan, and E.P. Salazar. 2013. Role of LOXs and COX-2 on FAK activation and cell migration induced by linoleic acid in MDA-MB-231 breast cancer cells. Cellular Oncology (Dordrecht) 36: 65–77. doi: 10.1007/s13402-012-0114-4.CrossRefGoogle Scholar
  215. Shi, H., M.V. Kokoeva, K. Inouye, I. Tzameli, H. Yin, and J.S. Flier. 2006. TLR4 links innate immunity and fatty acid-induced insulin resistance. The Journal of Clinical Investigation 116: 3015–3025. doi: 10.1172/JCI28898.PubMedPubMedCentralCrossRefGoogle Scholar
  216. Shimizu, C., T. Hasegawa, Y. Tani, F. Takahashi, M. Takeuchi, T. Watanabe, M. Ando, N. Katsumata, and Y. Fujiwara. 2004. Expression of insulin-like growth factor 1 receptor in primary breast cancer: Immunohistochemical analysis. Human Pathology 35: 1537–1542.PubMedCrossRefGoogle Scholar
  217. Simone, V., M. D’Avenia, A. Argentiero, C. Felici, F.M. Rizzo, G. De Pergola, and F. Silvestris. 2016. Obesity and breast cancer: Molecular interconnections and potential clinical applications. The Oncologist 21: 404–417. doi: 10.1634/theoncologist.2015-0351.PubMedPubMedCentralCrossRefGoogle Scholar
  218. Simpson, E.R., G.E. Ackerman, M.E. Smith, and C.R. Mendelson. 1981. Estrogen formation in stromal cells of adipose tissue of women: Induction by glucocorticosteroids. Proceedings of the National Academy of Sciences of the United States of America 78: 5690–5694.PubMedPubMedCentralCrossRefGoogle Scholar
  219. Slattery, M.L., K. Curtin, C. Sweeney, R.K. Wolff, R.N. Baumgartner, K.B. Baumgartner, A.R. Giuliano, and T. Byers. 2008. Modifying effects of IL-6 polymorphisms on body size-associated breast cancer risk. Obesity (Silver Spring, Md.) 16: 339–347. doi: 10.1038/oby.2007.44.CrossRefGoogle Scholar
  220. Soto-Guzman, A., N. Navarro-Tito, L. Castro-Sanchez, R. Martinez-Orozco, and E.P. Salazar. 2010. Oleic acid promotes MMP-9 secretion and invasion in breast cancer cells. Clinical & Experimental Metastasis 27: 505–515. doi: 10.1007/s10585-010-9340-1.CrossRefGoogle Scholar
  221. Stebbing, J., A. Sharma, B. North, T.J. Athersuch, A. Zebrowski, D. Pchejetski, R.C. Coombes, J.K. Nicholson, and H.C. Keun. 2012. A metabolic phenotyping approach to understanding relationships between metabolic syndrome and breast tumour responses to chemotherapy. Annals of Oncology 23: 860–866. doi: 10.1093/annonc/mdr347.PubMedCrossRefGoogle Scholar
  222. Subbaramaiah, K., L.R. Howe, P. Bhardwaj, B. Du, C. Gravaghi, R.K. Yantiss, X.K. Zhou, V.A. Blaho, T. Hla, P. Yang, L. Kopelovich, C.A. Hudis, and A.J. Dannenberg. 2011. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prevention Research (Philadelphia, Pa.) 4: 329–346. doi: 10.1158/1940-6207.CAPR-10-0381.CrossRefGoogle Scholar
  223. Subbaramaiah, K., P.G. Morris, X.K. Zhou, M. Morrow, B. Du, D. Giri, L. Kopelovich, C.A. Hudis, and A.J. Dannenberg. 2012. Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discovery 2: 356–365. doi: 10.1158/2159-8290.CD-11-0241.PubMedPubMedCentralCrossRefGoogle Scholar
  224. Subbaramaiah, K., E. Sue, P. Bhardwaj, B. Du, C.A. Hudis, D. Giri, L. Kopelovich, X.K. Zhou, and A.J. Dannenberg. 2013. Dietary polyphenols suppress elevated levels of proinflammatory mediators and aromatase in the mammary gland of obese mice. Cancer Prevention Research (Philadelphia, Pa.) 6: 886–897. doi: 10.1158/1940-6207.CAPR-13-0140.CrossRefGoogle Scholar
  225. Sulkowska, M., J. Golaszewska, A. Wincewicz, M. Koda, M. Baltaziak, and S. Sulkowski. 2006. Leptin—From regulation of fat metabolism to stimulation of breast cancer growth. Pathology & Oncology Research: POR 12: 69–72. doi:PAOR.2006.12.2.0069.
  226. Tan, J., E. Buache, M.-P. Chenard, N. Dali-Youcef, and M.-C. Rio. 2011. Adipocyte is a non-trivial, dynamic partner of breast cancer cells. The International Journal of Developmental Biology 55: 851–859. doi: 10.1387/ijdb.113365jt.PubMedCrossRefGoogle Scholar
  227. Tan, A., Y. Dang, G. Chen, and Z. Mo. 2015. Overexpression of the fat mass and obesity associated gene (FTO) in breast cancer and its clinical implications. International Journal of Clinical and Experimental Pathology 8: 13405–13410.PubMedPubMedCentralGoogle Scholar
  228. Thivat, E., S. Thérondel, O. Lapirot, C. Abrial, P. Gimbergues, E. Gadéa, E. Planchat, F. Kwiatkowski, M.A. Mouret-Reynier, P. Chollet, and X. Durando. 2010. Weight change during chemotherapy changes the prognosis in non metastatic breast cancer for the worse. BMC Cancer 10: 648. doi: 10.1186/1471-2407-10-648.PubMedPubMedCentralCrossRefGoogle Scholar
  229. Toft, D.J., and V.L. Cryns. 2011. Minireview: Basal-like breast cancer: From molecular profiles to targeted therapies. Molecular Endocrinology (Baltimore, Md.) 25: 199–211. doi: 10.1210/me.2010-0164.CrossRefGoogle Scholar
  230. Tomblin, J.K., and T.B. Salisbury. 2014. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells. Biochemical and Biophysical Research Communications 443: 1092–1096. doi: 10.1016/j.bbrc.2013.12.112.PubMedCrossRefGoogle Scholar
  231. Toniolo, P.G., M. Levitz, A. Zeleniuch-Jacquotte, S. Banerjee, K.L. Koenig, R.E. Shore, P. Strax, and B.S. Pasternack. 1995. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. Journal of the National Cancer Institute 87: 190–197.PubMedCrossRefGoogle Scholar
  232. Toropainen, E.M., P.K. Lipponen, and K.J. Syrjanen. 1995. Expression of insulin-like growth factor II in female breast cancer as related to established prognostic factors and long-term prognosis. Anticancer Research 15: 2669–2674.PubMedGoogle Scholar
  233. Tsuchida, A., T. Yamauchi, Y. Ito, Y. Hada, T. Maki, S. Takekawa, J. Kamon, M. Kobayashi, R. Suzuki, K. Hara, N. Kubota, Y. Terauchi, P. Froguel, J. Nakae, M. Kasuga, D. Accili, K. Tobe, K. Ueki, R. Nagai, and T. Kadowaki. 2004. Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. The Journal of Biological Chemistry 279: 30817–30822. doi: 10.1074/jbc.M402367200.PubMedCrossRefGoogle Scholar
  234. Turner, B.C., B.G. Haffty, L. Narayanan, J. Yuan, P.A. Havre, A.A. Gumbs, L. Kaplan, J.L. Burgaud, D. Carter, R. Baserga, and P.M. Glazer. 1997. Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Research 57: 3079–3083.PubMedGoogle Scholar
  235. Tworoger, S.S., A.H. Eliassen, T. Kelesidis, G.A. Colditz, W.C. Willett, C.S. Mantzoros, and S.E. Hankinson. 2007. Plasma adiponectin concentrations and risk of incident breast cancer. The Journal of Clinical Endocrinology and Metabolism 92: 1510–1516. doi: 10.1210/jc.2006-1975.PubMedCrossRefGoogle Scholar
  236. Uysal, K.T., S.M. Wiesbrock, M.W. Marino, and G.S. Hotamisligil. 1997. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389: 610–614. doi: 10.1038/39335.PubMedCrossRefGoogle Scholar
  237. Valle, A., J. Sastre-Serra, J. Oliver, and P. Roca. 2011. Chronic leptin treatment sensitizes MCF-7 breast cancer cells to estrogen. Cellular Physiology and Biochemistry. International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology 28: 823–832. doi: 10.1159/000335796.CrossRefGoogle Scholar
  238. van Kruijsdijk, R.C.M., E. van der Wall, and F.L.J. Visseren. 2009. Obesity and cancer: The role of dysfunctional adipose tissue. Cancer Epidemiology, Biomarkers & Prevention 18: 2569–2578. doi: 10.1158/1055-9965.EPI-09-0372.CrossRefGoogle Scholar
  239. Vandeweyer, E., and D. Hertens. 2002. Quantification of glands and fat in breast tissue: An experimental determination. Annals of Anatomy 184: 181–184. doi: 10.1016/S0940-9602(02)80016-4.PubMedCrossRefGoogle Scholar
  240. Vedin, L.-L., S.A. Lewandowski, P. Parini, J.-A. Gustafsson, and K.R. Steffensen. 2009. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis 30: 575–579. doi: 10.1093/carcin/bgp029.PubMedCrossRefGoogle Scholar
  241. Vigushin, D.M., Y. Dong, L. Inman, N. Peyvandi, J.P. Alao, C. Sun, S. Ali, E.J. Niesor, C.L. Bentzen, and R.C. Coombes. 2004. The nuclear oxysterol receptor LXRalpha is expressed in the normal human breast and in breast cancer. Medical Oncology (Northwood, London, England) 21: 123–131. doi: 10.1385/MO:21:2:123.CrossRefGoogle Scholar
  242. Vona-Davis, L., and D.P. Rose. 2013. The obesity-inflammation-eicosanoid axis in breast cancer. Journal of Mammary Gland Biology and Neoplasia 18: 291–307. doi: 10.1007/s10911-013-9299-z.PubMedCrossRefGoogle Scholar
  243. Vozarova, B., C. Weyer, K. Hanson, P.A. Tataranni, C. Bogardus, and R.E. Pratley. 2001. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obesity Research 9: 414–417. doi: 10.1038/oby.2001.54.PubMedCrossRefGoogle Scholar
  244. Vrieling, A., K. Buck, R. Kaaks, and J. Chang-Claude. 2010. Adult weight gain in relation to breast cancer risk by estrogen and progesterone receptor status: A meta-analysis. Breast Cancer Research and Treatment 123: 641–649. doi: 10.1007/s10549-010-1116-4.PubMedCrossRefGoogle Scholar
  245. Wang, Z., X. Zhang, P. Shen, B.W. Loggie, Y. Chang, and T.F. Deuel. 2005. Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66. Biochemical and Biophysical Research Communications 336: 1023–1027. doi: 10.1016/j.bbrc.2005.08.226.PubMedCrossRefGoogle Scholar
  246. Wang, J., D.-L. Yang, Z.-Z. Chen, and B.-F. Gou. 2016. Associations of body mass index with cancer incidence among populations, genders, and menopausal status: A systematic review and meta-analysis. Cancer Epidemiology 42: 1–8. doi: 10.1016/j.canep.2016.02.010.PubMedCrossRefGoogle Scholar
  247. Weisberg, S.P., D. McCann, M. Desai, M. Rosenbaum, R.L. Leibel, and A.W. Ferrante. 2003. Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation 112: 1796–1808. doi: 10.1172/JCI19246.PubMedPubMedCentralCrossRefGoogle Scholar
  248. Wolowczuk, I., C. Verwaerde, O. Viltart, A. Delanoye, M. Delacre, B. Pot, and C. Grangette. 2008. Feeding our immune system: Impact on metabolism. Clinical & Developmental Immunology 2008: 639803. doi: 10.1155/2008/639803.CrossRefGoogle Scholar
  249. Won, H.S., Y.A. Kim, J.S. Lee, E.K. Jeon, H.J. An, D.S. Sun, Y.H. Ko, and J.S. Kim. 2013. Soluble interleukin-6 receptor is a prognostic marker for relapse-free survival in estrogen receptor-positive breast cancer. Cancer Investigation 31: 516–521. doi: 10.3109/07357907.2013.826239.PubMedCrossRefGoogle Scholar
  250. Wu, Q., T. Ishikawa, R. Sirianni, H. Tang, J.G. McDonald, I.S. Yuhanna, B. Thompson, L. Girard, C. Mineo, R.A. Brekken, M. Umetani, D.M. Euhus, Y. Xie, and P.W. Shaul. 2013. 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Reports 5: 637–645. doi: 10.1016/j.celrep.2013.10.006.PubMedPubMedCentralCrossRefGoogle Scholar
  251. Yao-Borengasser, A., B. Monzavi-Karbassi, R.A. Hedges, L.J. Rogers, S.A. Kadlubar, and T. Kieber-Emmons. 2015. Adipocyte hypoxia promotes epithelial-mesenchymal transition-related gene expression and estrogen receptor-negative phenotype in breast cancer cells. Oncology Reports 33: 2689–2694. doi: 10.3892/or.2015.3880.PubMedPubMedCentralGoogle Scholar
  252. Ye, J., J. Jia, S. Dong, C. Zhang, S. Yu, L. Li, C. Mao, D. Wang, J. Chen, and G. Yuan. 2014. Circulating adiponectin levels and the risk of breast cancer: A meta-analysis. European Journal of Cancer Prevention 23: 158–165. doi: 10.1097/CEJ.0b013e328364f293.PubMedCrossRefGoogle Scholar
  253. Yerushalmi, R., K.A. Gelmon, S. Leung, D. Gao, M. Cheang, M. Pollak, G. Turashvili, B.C. Gilks, and H. Kennecke. 2012. Insulin-like growth factor receptor (IGF-1R) in breast cancer subtypes. Breast Cancer Research and Treatment 132: 131–142. doi: 10.1007/s10549-011-1529-8.PubMedCrossRefGoogle Scholar
  254. Yonezawa, T., K. Katoh, and Y. Obara. 2004. Existence of GPR40 functioning in a human breast cancer cell line, MCF-7. Biochemical and Biophysical Research Communications 314: 805–809.PubMedCrossRefGoogle Scholar
  255. Yoon, J.-H., J.K. Park, S.S. Oh, K.-H. Lee, S.-K. Kim, I.-J. Cho, J.-K. Kim, H.-T. Kang, S.G. Ahn, J.-W. Lee, S.-H. Lee, A. Eom, J.-Y. Kim, S.V. Ahn, and S.B. Koh. 2011. The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: The Korean Genomic Rural Cohort Study. Clinica Chimica Acta: International Journal of Clinical Chemistry 412: 2199–2205. doi: 10.1016/j.cca.2011.08.003.CrossRefGoogle Scholar
  256. Yue, W., J.-P. Wang, Y. Li, W.P. Bocchinfuso, K.S. Korach, P.D. Devanesan, E. Rogan, E. Cavalieri, and R.J. Santen. 2005. Tamoxifen versus aromatase inhibitors for breast cancer prevention. Clinical Cancer Research 11: 925s–930s.PubMedGoogle Scholar
  257. Zhang, G.J., and I. Adachi. 1999. Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Research 19: 1427–1432.PubMedGoogle Scholar
  258. Zhang, X.-T., L. Ding, L.-G. Kang, and Z.-Y. Wang. 2012. Involvement of ER-α36, Src, EGFR and STAT5 in the biphasic estrogen signaling of ER-negative breast cancer cells. Oncology Reports 27: 2057–2065. doi: 10.3892/or.2012.1722.PubMedPubMedCentralGoogle Scholar
  259. Zhou, W., S. Guo, and R.R. Gonzalez-Perez. 2011. Leptin pro-angiogenic signature in breast cancer is linked to IL-1 signalling. British Journal of Cancer 104: 128–137. doi: 10.1038/sj.bjc.6606013.PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of General SurgeryGazi UniversityBesevlerTurkey
  2. 2.CankayaTurkey

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