ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/2071-8713-3859ometendo-3859Research ArticleСтатьиArticlesПерспективы в лечении рака молочной железы у женщин в постменопаузе с избыточной массой тела и ожирениемPerspectives in the treatment of breast cancer in postmenopausal women who are overweight and obeseTroshinaEkaterina Anatol'evna

д.м.н., проф., зав отд. терапии и патологии метаболизма, ФГБУ Эндокринологический научный центр Минздрава РФ, Москва

troshina@inbox.ruRumyantsevPavel Olegovich

д.м.н., ФГБУ Эндокринологический научный центр Минздрава РФ, Москва

rumyantsev@endocrincentr.ruAltashinaM V

аспирант, ФГБУ Эндокринологический научный центр Минздрава РФ, Москва

alt-mar@mail.ruPlokhayaAnna A

к.м.н., ФГБУ Эндокринологический научный центр Минздрава РФ, Москва

plokhaya@bk.ruЭндокринологический научный центрRussian Federation201330102013103№3 (2013)310Copyright © Troshina E.A., Rumyantsev P.O., Altashina M.V., Plokhaya A.A., 20132013Troshina E.A., Rumyantsev P.O., Altashina M.V., Plokhaya A.A.Troshina E.A., Rumyantsev P.O., Altashina M.V., Plokhaya A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/3859

Избыточная масса тела и ожирение у женщин в постменопаузе являются факторами риска развития рака молочной железы. Выявление особенностей патогенеза заболевания у данной группы пациенток привело к появлению новых направлений в лечении и профилактике. В статье представлены данные о противораковом действии метформина, нестероидных противовоспалительных препаратов и витамина D.

Overweight and obesity in postmenopausal women are risk factors for breast cancer. Identifying features of the pathogenesis of the disease in this group of patients has led to the emergence of new trends in treatment and prevention. The article presents data on the anti-cancer effects of metformin, nonsteroidal anti-inflammatory drugs and vitamin D

рак молочной железыожирениегиперинсулинемияметформиннестероидные противовоспалительные препаратыаспиринвитамин Dbreast cancerobesityhyperinsulinemiametforminnonsteroidal anti-inflammatory drugsaspirinvitamin DReferencesДедов И.И., Мельниченко Г.А. (ред.) Эндокринология. Национальное руководство. М.: Гэотар-Медиа, 2009: 209.Дедов И.И., Мельниченко Г.А. (ред.) Эндокринология. Национальное руководство. М.: Гэотар-Медиа, 2009: 209.Alfonso LF, Srivenugopal KS, Arumugam TV, Abbruscato TJ, Weidanz JA, Bhat GJ. Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells. International Journal of Oncology. 2009; 34(3): 597–608.Alfonso LF, Srivenugopal KS, Arumugam TV, Abbruscato TJ, Weidanz JA, Bhat GJ. Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells. International Journal of Oncology. 2009; 34(3): 597–608.Anisimov VN. Metformin for aging and cancer prevention. Aging. 2010; 2(11): 760–774.Anisimov VN. Metformin for aging and cancer prevention. Aging. 2010; 2(11): 760–774.Begoсa MC, Vazquez-Martin A, Oliveras-Ferraros C and Menendez JA. Metformin and cancer Doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle. 2010; 9(6): 1057–1054.Begoсa MC, Vazquez-Martin A, Oliveras-Ferraros C and Menendez JA. Metformin and cancer Doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle. 2010; 9(6): 1057–1054.Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, et al. Plasma 25 hydoxyvitamin D and 1,25 hydroxyvitamin D and risk of breast cancer. Cancer Epidemiology, Biomarkers and Prevention. 2005; 14: 1991–1997.Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, et al. Plasma 25 hydoxyvitamin D and 1,25 hydroxyvitamin D and risk of breast cancer. Cancer Epidemiology, Biomarkers and Prevention. 2005; 14: 1991–1997.Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. The New England Journal of Medicine. 2003; 348: 1625–1638.Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. The New England Journal of Medicine. 2003; 348: 1625–1638.Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T. Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proceedings of the National Academy of Sciences. 2004; 101: 591–596.Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T. Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proceedings of the National Academy of Sciences. 2004; 101: 591–596.Chong CR and Chabner BA. Mysterious Metformin. Оncologist. 2009; 14(12): 1178–1181.Chong CR and Chabner BA. Mysterious Metformin. Оncologist. 2009; 14(12): 1178–1181.Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. Journal of Clinical Oncology. 2002; 20: 1128–1143.Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. Journal of Clinical Oncology. 2002; 20: 1128–1143.Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O'Sullivan MJ, Yasmeen S, Hiatt RA, Shikany JM, Vitolins M, Khandekar J, Hubbell FA. Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of breast cancer. Journal of the National Cancer Institite. 2008; 100: 1581–1591.Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O'Sullivan MJ, Yasmeen S, Hiatt RA, Shikany JM, Vitolins M, Khandekar J, Hubbell FA. Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of breast cancer. Journal of the National Cancer Institite. 2008; 100: 1581–1591.Crawford YG, Gauthier ML, Joubel A, Mantei K, Kozakiewicz K, Afshari CA, Tlsty TD. Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell. 2004; 5: 263–273.Crawford YG, Gauthier ML, Joubel A, Mantei K, Kozakiewicz K, Afshari CA, Tlsty TD. Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell. 2004; 5: 263–273.Cui Y, Whiteman MK, Flaws JA, et al. Body mass and stage of breast cancer at diagnosis. International Journal of Cancer. 2002; 98: 279–283.Cui Y, Whiteman MK, Flaws JA, et al. Body mass and stage of breast cancer at diagnosis. International Journal of Cancer. 2002; 98: 279–283.Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Natural Reviews Cancer. 2007; 7: 684–700.Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Natural Reviews Cancer. 2007; 7: 684–700.Dormanen MC, Bishop JE, Hammond MW, Okamura WH, Nemere I, Norman AW. Nonnuclear effects of the steroid hormone 1 alpha,25(OH)2-vitamin D3: analogs are able to functionally differentiate between nuclear and membrane receptors. Biochemical and Biophysical Research Communications. 1994; 201: 394–401.Dormanen MC, Bishop JE, Hammond MW, Okamura WH, Nemere I, Norman AW. Nonnuclear effects of the steroid hormone 1 alpha,25(OH)2-vitamin D3: analogs are able to functionally differentiate between nuclear and membrane receptors. Biochemical and Biophysical Research Communications. 1994; 201: 394–401.Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988; 240: 889–895.Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988; 240: 889–895.Ewertz M, Jensen M-B, Gunnarsdóttir KA, et al. Effect of obesity on prognosis after early-stage breast cancer. Journal of Clinical Oncology. 2011; 29: 25–31.Ewertz M, Jensen M-B, Gunnarsdóttir KA, et al. Effect of obesity on prognosis after early-stage breast cancer. Journal of Clinical Oncology. 2011; 29: 25–31.Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxy vitamin D levels in early breast cancer. Journal of Clinical Oncology. 2009; 27: 3757–63.Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxy vitamin D levels in early breast cancer. Journal of Clinical Oncology. 2009; 27: 3757–63.Grano M, Mori G, Minielli V, Cantatore FP, Colucci S, Zallone AZ. Breast cancer cell line MDA-231 stimulates osteoclastogenesis and bone resorption in human osteoclasys. Boichemical and Biophysical Research Communications. 2000; 270: 1097–1100.Grano M, Mori G, Minielli V, Cantatore FP, Colucci S, Zallone AZ. Breast cancer cell line MDA-231 stimulates osteoclastogenesis and bone resorption in human osteoclasys. Boichemical and Biophysical Research Communications. 2000; 270: 1097–1100.Harris RE, Kasbari S, Farrar WB. Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer. Oncology Reports. 1998; 6(1): 71–73.Harris RE, Kasbari S, Farrar WB. Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer. Oncology Reports. 1998; 6(1): 71–73.Hirsch AH, Iliopoulos D, Tsichlis NP and Struhl K. Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission. Cancer Research. 2009; 69(19): 7507–7511.Hirsch AH, Iliopoulos D, Tsichlis NP and Struhl K. Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission. Cancer Research. 2009; 69(19): 7507–7511.Herschman HR. Prostaglandin synthase. Biochimica et Biophysica Acta. 1996; 1299: 125–140.Herschman HR. Prostaglandin synthase. Biochimica et Biophysica Acta. 1996; 1299: 125–140.Howe LR. Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Research. 2007; 9(4): 210.Howe LR. Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Research. 2007; 9(4): 210.Imtiaz S, Siddiqui N, Raza SA, Loya A, Muhammad A. Vitamin D deficiency in newly diagnosed breast cancer patients. Indian Journal of Endocrinology and Metabolism. 2012; 16(3): 409–413.Imtiaz S, Siddiqui N, Raza SA, Loya A, Muhammad A. Vitamin D deficiency in newly diagnosed breast cancer patients. Indian Journal of Endocrinology and Metabolism. 2012; 16(3): 409–413.Jacobs EJ, Thun MJ, Bain EB, Rodriguez C, Henley SJ, Calle EE. A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. Journal of the National Cancer Institute. 2007; 99(8): 608–615.Jacobs EJ, Thun MJ, Bain EB, Rodriguez C, Henley SJ, Calle EE. A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. Journal of the National Cancer Institute. 2007; 99(8): 608–615.Janowsky EC, Lester GE, Weinberg CR, Millikan RC, Schildkraut JM, Garrett PA, Hulka BS. Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutrition. 1999; 2: 283–291.Janowsky EC, Lester GE, Weinberg CR, Millikan RC, Schildkraut JM, Garrett PA, Hulka BS. Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutrition. 1999; 2: 283–291.Jiralesprong S, Gonzalez-Angulo AM, Hung MC Expanding the arsenal: metformin for the treatment of triple-negative breast cancer? Cell Cycle. 2009; 8(17): 2682.Jiralesprong S, Gonzalez-Angulo AM, Hung MC Expanding the arsenal: metformin for the treatment of triple-negative breast cancer? Cell Cycle. 2009; 8(17): 2682.Jiralerspong S, Palla SL, Giordano SH, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. Journal of Clinical Oncology. 2009; 27(20): 3297–3302.Jiralerspong S, Palla SL, Giordano SH, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. Journal of Clinical Oncology. 2009; 27(20): 3297–3302.Johnson TW, Anderson KE, Lazovich D, Folsom AR. Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiology Biomarkers and Prevention. 2002; 11(12): 1586–1591.Johnson TW, Anderson KE, Lazovich D, Folsom AR. Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiology Biomarkers and Prevention. 2002; 11(12): 1586–1591.Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, Funahashi T, Matsuzava Y. Selective supressionof endothelial cell apoptosis by the high molecular weight form of adiponectin. Circulation Research. 2004; 94: 27–31.Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, Funahashi T, Matsuzava Y. Selective supressionof endothelial cell apoptosis by the high molecular weight form of adiponectin. Circulation Research. 2004; 94: 27–31.Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Viatmin D and calcium supplementation reduces cancer risk: Results of a randomized trial. The American Journal of Clinical Nutrition. 2007; 85: 1586–91.Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Viatmin D and calcium supplementation reduces cancer risk: Results of a randomized trial. The American Journal of Clinical Nutrition. 2007; 85: 1586–91.Lorincz AM, Sukumar S. Molecular links between obesity and breast cancer. Endocrine-Related Cancer. 2006; 13: 179–292.Lorincz AM, Sukumar S. Molecular links between obesity and breast cancer. Endocrine-Related Cancer. 2006; 13: 179–292.Macciò A, Madeddu C. Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications. Scientific World Journal. 2011; 11: 2020–2036.Macciò A, Madeddu C. Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications. Scientific World Journal. 2011; 11: 2020–2036.Majed B, Moreau T, Senouci K, et al. Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Research and Treatment. 2008; 111: 329–342.Majed B, Moreau T, Senouci K, et al. Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Research and Treatment. 2008; 111: 329–342.Marshall SF, Bernstein L, Anton-Culver H, et al. Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. Journal of the National Cancer Institute. 2005; 97(11): 805–812.Marshall SF, Bernstein L, Anton-Culver H, et al. Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. Journal of the National Cancer Institute. 2005; 97(11): 805–812.Martinez J, Cifuentes M. Adipose Tissue and Desmoplastic Response in Breast Cancer. Breast Cancer – Carcinogenesis, Cell Growth and Signalling Pathways. 2011, InTech: 447–456.Martinez J, Cifuentes M. Adipose Tissue and Desmoplastic Response in Breast Cancer. Breast Cancer – Carcinogenesis, Cell Growth and Signalling Pathways. 2011, InTech: 447–456.Mawer EB, Walls J, Howell A, Davies M, Ratcliffe WA, Bundred NJ. Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases. Journal of Clinical Endocrinology and Metabolism. 1997; 82: 118–122.Mawer EB, Walls J, Howell A, Davies M, Ratcliffe WA, Bundred NJ. Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases. Journal of Clinical Endocrinology and Metabolism. 1997; 82: 118–122.Muti P, Berrino F, Krogh V, Villarini A, Barba M, Strano S, Blandino G. Metformin, diet and breast cancer An avenue for chemoprevention. Cell Cycle. 2009; 8(16): 2661–2661.Muti P, Berrino F, Krogh V, Villarini A, Barba M, Strano S, Blandino G. Metformin, diet and breast cancer An avenue for chemoprevention. Cell Cycle. 2009; 8(16): 2661–2661.Napoli N, Vattikuti S, Ma C, Rastelli A, Rayani A, Donepudi R, et al. High prevalence of low vitamin D and musculoskeletal complaints in women with breast cancer. The Breast Journal. 2010; 16: 609–16.Napoli N, Vattikuti S, Ma C, Rastelli A, Rayani A, Donepudi R, et al. High prevalence of low vitamin D and musculoskeletal complaints in women with breast cancer. The Breast Journal. 2010; 16: 609–16.Petroulakis E, Mamane Y, Le Bacquer O, Shahbazian D, Sonenberg N. mTOR signaling: implications for cancer and anticancer therapy. British Journal of Cancer. 2006; 94: 195–9.Petroulakis E, Mamane Y, Le Bacquer O, Shahbazian D, Sonenberg N. mTOR signaling: implications for cancer and anticancer therapy. British Journal of Cancer. 2006; 94: 195–9.Phoenix KN, Vumbaca F, Claffey KP. Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERα negative MDA-MB-435 breast cancer model. Breast Cancer Research and Treatment. 2009; 113(1): 101–111.Phoenix KN, Vumbaca F, Claffey KP. Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERα negative MDA-MB-435 breast cancer model. Breast Cancer Research and Treatment. 2009; 113(1): 101–111.Prosperi JR, Robertson FM. 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 and Other Lipid Mediators. 2006; 81: 55–70.Prosperi JR, Robertson FM. 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 and Other Lipid Mediators. 2006; 81: 55–70.Rainville C, Khan Y, Tisman G. Triple negative breast cancer patients presenting with low serum vitamin D levels: a case series. Cases Journal. 2009; 2: 83–90.Rainville C, Khan Y, Tisman G. Triple negative breast cancer patients presenting with low serum vitamin D levels: a case series. Cases Journal. 2009; 2: 83–90.Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Research. 2002; 62: 632–635.Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Research. 2002; 62: 632–635.Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. Journal of Clinical Oncology. 2010; 28: 3411–3415.Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. Journal of Clinical Oncology. 2010; 28: 3411–3415.Shackelford DB, Shaw RG. The LKB1-AMPK pathway: metabolism and growth control in tumor suppression. Nature Reveiws cancer. 2009; 9(8): 563–675.Shackelford DB, Shaw RG. The LKB1-AMPK pathway: metabolism and growth control in tumor suppression. Nature Reveiws cancer. 2009; 9(8): 563–675.Shao T, Klein P and Grossbard ML. Vitamin D and Breast Cancer. Oncologist. 2012; 17(1): 36–45.Shao T, Klein P and Grossbard ML. Vitamin D and Breast Cancer. Oncologist. 2012; 17(1): 36–45.Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willet WC. Intake of dairy products, calcium and vitamin D and risk of breast cancer. Journal of the National Cancer Institute. 2002; 94: 1301–11.Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willet WC. Intake of dairy products, calcium and vitamin D and risk of breast cancer. Journal of the National Cancer Institute. 2002; 94: 1301–11.Slattery ML, Sweeney C, Wolff R, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Research and Treatment. 2007; 104(2): 197–209.Slattery ML, Sweeney C, Wolff R, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Research and Treatment. 2007; 104(2): 197–209.Takkouche B, Regueira-Méndez C, Etminan M. Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Journal of the National Cancer Institute. 2008; 100(20): 1439–1447.Takkouche B, Regueira-Méndez C, Etminan M. Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Journal of the National Cancer Institute. 2008; 100(20): 1439–1447.Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. Journal of the American Medical Association. 2004; 291: 2433–2440.Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. Journal of the American Medical Association. 2004; 291: 2433–2440.Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circulation Research. 2007; 100: 328–41.Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circulation Research. 2007; 100: 328–41.Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. British Journal of Nutrition. 2004; 92(3): 347–55.Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. British Journal of Nutrition. 2004; 92(3): 347–55.Van der Rhee H, Coebergh JW, de Vries E. Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies. European Journal of Cancer Prevention. 2009; 18: 458–75.Van der Rhee H, Coebergh JW, de Vries E. Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies. European Journal of Cancer Prevention. 2009; 18: 458–75.Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009; 8(1): 88–96.Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009; 8(1): 88–96.Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley LE. Circulating interleukin-6 in relation to adiposity, insukin action, and insulin secretion. Obesity Research. 2001; 9: 414–417.Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley LE. Circulating interleukin-6 in relation to adiposity, insukin action, and insulin secretion. Obesity Research. 2001; 9: 414–417.Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999; 18: 7908–7916.Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999; 18: 7908–7916.Yee D, Lee AV. Crosstalk between the insulin-like growth factors and estrogens in breast cancer. Journal Mammary Gland Biology and Neuplasia. 2000; 5: 107–115.Yee D, Lee AV. Crosstalk between the insulin-like growth factors and estrogens in breast cancer. Journal Mammary Gland Biology and Neuplasia. 2000; 5: 107–115.Zinser G, Packman K, Welsh J. Vitamin D(3) receptor ablation alters mammary gland morphogenesis. Development. 2002; 129: 3067–3076.Zinser G, Packman K, Welsh J. Vitamin D(3) receptor ablation alters mammary gland morphogenesis. Development. 2002; 129: 3067–3076.

The authors declare that there are no conflicts of interest present.