Background: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. Methods: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. Results: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. Conclusion: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

1.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, International Agency for Research on Cancer, 2013.
2.
Konecny G, Pauletti G, Pegram M, Untch M, Dandekar S, Aguilar Z, et al: Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 2003;95:142-153.
3.
Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, et al: Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 2010;28:509-518.
4.
Longcope C, Baker R, Johnston CC Jr: Androgen and estrogen metabolism: relationship to obesity. Metabolism 1986;35:235-237.
5.
Catalano S, Marsico S, Giordano C, Mauro L, Rizza P, Panno ML, et al: Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. J Biol Chem 2003;278:28668-28676.
6.
Lu Q, Nakmura J, Savinov A, Yue W, Weisz J, Dabbs D, et al: Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers. Endocrinology 1996;137:3061-3068.
7.
Brodie AM, Nijar VC: Aromatase inhibitors and breast cancer. Semin Oncol 1996;23(4 suppl 9):10-20.
8.
Love RR, Barden HS, Mazess RB, Epstein S, Chappel RJ: Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med 1994;154:2585-2588.
9.
Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM, et al: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 1994;86:527-537.
10.
Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, et al: Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 2003;95:1218-1226.
11.
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295.
12.
Sonnenberg GE, Krakower GR, Hoffmann RG, Maas DL, Hennes MI, Kıssebah AH: Plasma leptin concentrations during extended fasting and graded glucose infusions: relationships with changes in glucose, insulin, and FFA. J Clin Endocrinol Metab 2001;86:4895-4900.
13.
Haffner SM, Gingerich RL, Miettinen H, Stern MP: Leptin concentration in relation to overall adiposity and regional body fat distribution in Mexican Americans. Int J Obes Relat Metab Disord 1996;20:904-908.
14.
Zimmet P, Hodge A, Nicolson M, Staten M, de Courten M, Moore J, et al: Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ 1996;313:965-969.
15.
Bennett FI, McFarlane-Anderson N, Wilks R, Luke A, Cooper RS, Forrester TE: Leptin concentration in women is influenced by regional distribution of adipose tissue. Am J Clin Nutr 1997;66:1340-1344.
16.
Bray GA, York DA: Leptin and clinical medicine: a new piece in the puzzle of obesity. J Clin Endocrinol Metab 1997;82:2771-2776.
17.
Casabiell X, Pineiro V, Peino R, Lage M, Camina J, Gallego R, et al: Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men. J Clin Endocrinol Metab 1998;83:2149-2155.
18.
Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato N: Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol 1997;154:285-292.
19.
Jarde T, Caldefie-Chezet F, Goncalves-Mendes N, Mishellany F, Buechler C, Penault-Liorca F, et al: Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies. Endocr Relat Cancer 2009;16:1197-1210.
20.
Vona-Davis L, Rose DP: Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 2007;14:189-206.
21.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930-1935.
22.
Christiansen T, Paulsen SK, Bruun JM, Ploug T, Richelsen B, Pedersen SB: Diet-induced weight loss and exercise alone and in combination enhance the expression of adiponectin receptors in adipose tissue and skeletal muscle, but only diet-induced weight loss enhanced circulating adiponectin. J Clin Endocrinol Metab 2010;95:911-919.
23.
Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, et al: Adiponectin and breast cancer risk. J Clin Endocrinol Metab 2004;89:1102-1107.
24.
Man K, Ng KT, Xu A, Cheng Q, Lo CM, Xiao JW, et al: Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling. Clin Cancer Res 2010;16:967-977.
25.
Wang Y, Lam JB, Lam KS, Liu J, Lam MC, Hoo RL, et al: Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res 2006;66:11462-11470.
26.
Ryan AS, Berman DM, Nicklas BJ, Sınha M, Gıngerıch RL, Meneılly GS, et al: Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity. Diabetes Care 2003;26:2383-2388.
27.
Vona-Davis L, Rose DP: Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 2007;14:189-206.
28.
Cleary MP, Ray A, Rogozina OP, Dogan S, Grossmann ME: Targeting the adiponectin:leptin ratio for postmenopausal breast cancer prevention. Front Biosci (Schol Ed) 2009;1:329-357.
29.
Lee CC, Kasa-Vubu JZ, Supiano MA: Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women. J Am Geriatr Soc 2003;51:683-688.
30.
Francucci CM, Daniele P, Iori N, Camilletti A, Massi F, Boscaro M: Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women. J Endocrinol Invest 2005;28:623-631.
31.
Jacobsen DE, Samson MM, Emmelot-Vonkand MH, Verhaar HJJ: Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial. Eur J Endocrinol 2010;162:371-376.
32.
Tommaselli GA, Di Carlo C, Di Spiezio Sardo A, Bifulco G, Cirillo D, Guida M, et al: Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene. Menopause 2006;13:660-668.
33.
Nguyen MC, Stewart RB, Banerji MA, Gordon DH, Kral JG: Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer. Int J Obes Relat Metab Disord 2001;25:296-298.
34.
Grey A, Stapleton J, Evans M, Reid I: The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women. J Clin Endocrinol Metab 1995;80:3191-3195.
35.
Dunnwald LK, Rossing MA, Li CI: Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 2007;9:R6.
36.
van Londen GJ, Perera S, Vujevich K, Rastogi P, Lembersky B, Brufsky A, et al: The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer. Breast Cancer Res Treat 2011;125:441-446.
37.
Francini G, Petrioli R, Montagnani A, Cadirni A, Campagna S, Francini E, et al: Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids. Br J Cancer 2006;95:153-158.
38.
Lorincz AM, Sukumar S: Molecular links between obesity and breast cancer. Endocr Relat Cancer 2006;13:279-292.
39.
Moon HS, Dalamaga M, Kim SY, Polyzos SA, Hamnvik OP, Magkos F: Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr Rev 2013;34:377-412.
40.
Catalano S, Mauro L, Bonofiglio D, Pellegrino M, Qi H, Rizza P: In vivo and in vitro evidence that PPARγ ligands are antagonists of leptin signaling in breast cancer. Am J Pathol 2011;179:1030-1040.
41.
Ray A: Adipokine leptin in obesity-related pathology of breast cancer. J Biosci 2012;37:289-294.
42.
Grossmann ME, Cleary MP: The balance between leptin and adiponectin in the control of carcinogenesis - focus on mammary tumorigenesis. Biochimie 2012;94:2164-2171.
43.
Dalamaga M, Diakopoulos KN, Mantzoros CS: The role of adiponectin in cancer: a review of current evidence. Endocr Rev 2012;33:547-594.
44.
Delort L, Jardé T, Dubois V, Vasson MP, Caldefie-Chézet F: New insights into anticarcinogenic properties of adiponectin: a potential therapeutic approach in breast cancer? Vitam Horm 2012;90:397-417.
45.
Macis D, Gandini S, Guerrieri-Gonzaga A, Johansson H, Magni P, Ruscica M, et al: Prognostic effect of circulating adiponectin in a randomized 2 × 2 trial of low-dose tamoxifen and fenretinide in premenopausal women at risk for breast cancer. J Clin Oncol 2012;30:151-157.
46.
Marttunen MB, Anderson S, Hietanen P, Karonen S, Koistinen HA, Koivisto VA, et al: Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients. Maturitas 2000;35:175-179.
47.
Ozet A, Arpaci F, Yilmaz MI, Ayta H, Ozturk B, Komurcu Ş, et al: Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol 2001;31:424-427.
48.
Geisler J, Ekse D, Lonning P: The aromatase inactivator exemestane decreases plasma leptin levels in postmenopausal breast cancer patients (abstract 420). 97th Annu Meet Am Assoc Cancer Res, Washington, 2006.
49.
Huang Z, Willett WC, Colditz GA, Hunter DJ, Manson JE, Rosner B, et al: Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses' Health Study. Am J Epidemiol 1999;150:1316-1324.
50.
Lahmann PH, Hoffmann K, Allen N, van Gils CH, Khaw KT, Tehard B, et al: Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 2004;111:762-771.
51.
Garaulet M, Perez-Llamas F, Baraza JC, Garcia-Prieto MD, Fardy PS, Tebar FJ, et al: Body fat distribution in pre- and post-menopausal women: metabolic and anthropometric variables. J Nutr Health Aging 2002;6:123-126.
52.
Valsamakis G, Chetty R, Anwar A, Banerjee AK, Barnett A, Kumar S: Association of simple anthropometric measures of obesity with visceral fat and the metabolic syndrome in male Caucasian and Indo-Asian subjects. Diabet Med 2004;21:1339-1345.
53.
Chen DC, Chung YF, Yeh YT, Chaung HC, Kuo FC, Fu OY, et al: Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett 2006;237:109-114.
54.
Grossmann ME, Ray A, Dogan S, Mizuno NK, Cleary MP: Balance of adiponectin and leptin modulates breast cancer cell growth. Cell Res 2008;18:1154-1156.
55.
Cleary MP, Ray A, Rogozina OP, Dogan S, Grossmann ME: Targeting the adiponectin:leptin ratio for postmenopausal breast cancer prevention. Front Biosci 2009;S1:329-335.
56.
Hu FB, Chen C, Wang B, Stampfer MJ, Xu X: Leptin concentrations in relation to overall adiposity, fat distribution, and blood pressure in a rural Chinese population. Int J Obes Relat Metab Disord 2001;25:121-125.
57.
Ostlund RE, Yang JW, Klein S, Gingerich R: Relation between plasma leptin concentration and body fat, gender, diet, age and metabolic covariates. J Clin Endocrinol Metab 1996;81:3909- 3913.
58.
Barb D, Williams CJ, Neuwirth AK, Mantzoros CS: Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr 2007;86:858-866.
59.
Ziemke F, Mantzoros CS: Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr 2010;91:258-261.
60.
Lapauw B, Sjoen GT, Mahmoud A, Kaufman JM, Ruige JB: Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men. Eur J Endocrinol 2009;160:397-402.
61.
Morad V, Abrahamsson A, Dabrosin C: Estradiol affects extracellular leptin:adiponectin ratio in human breast tissue in vivo. J Clin Endocrinol Metab 2014;99:3460-3467.
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