Metabolic syndrome and breast cancer: a dangerous association for postmenopausal women
A postmenopausal women prevention study
Keywords:
breast cancer, metabolic syndrome, metabolic cardiomyopathy, postmenopausal womenAbstract
Background:
Breast cancer(BC) is the most common cancer in women worldwide, the relationship between metabolic syndrome(MetS) and BC needs to be better clarified. Today the early diagnosis of breast cancer(BC) is yet a challenging problem in clinical practice, so the evidence that a well identified population of postmenopausal women, affected by MetS, presents a high risk, of breast cancer occurrence, is useful for breast cancer prevention. Our study aims to assess the prevalence of metabolic syndrome, diagnosed according to current guidelines, in postmenopausal women with breast cancer, and its role as an independent risk factor.
Results:
MetS rate was significantly higher among women affected by BC:10.1%, 33 women, than CG:5.4%, 18 women, Chi-squared4.8,Odds ratio1.94,c.i.95%,p<0.02. Metabolic cardiomyopathy rate was significantly higher among women affected by BC:5.8%, 18 women, than CG:1.8%, 6 women, Chi-squared6.5,Odds ratio3.2,c.i.95%,p<0.01. Otherwise MetS rate without cardiomyopathy was higher among women affected by BC:4.8%, 15 women, than CG:3.4%, 11 women, but in a not statistically significant way, Chi-squared0.8,Odds ratio1.35,c.i.95%,p<0.36.
Conclusion:
There was a significant relationship, in our population, between MetS and BC, adding evidence to this controversial association, the relationship was even tighter, when restricted to women affected by metabolic cardiomyopathy; otherwise it, restricted to women affected by MetS, without metabolic cardiomyopathy, was not statistically significant. Since the prevalence of MetS is increasing worldwide, just like the incidence of BC, an intervention is needed to improve physical activity and weight reduction to decrease the MetS rate.
References
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29. Palmiero P, Zito A, Maiello M, Cameli M, Modesti PA, Muiesan ML, et al. Left Ventricular Diastolic Function in Hypertension: Methodological Considerations and Clinical Implications. J Clin Med Res [Internet]. 2015 [cited 2021 Jan 10];7(3):137–44. Available from: https://pubmed.ncbi.nlm.nih.gov/25584097/
30. Palmiero P, Maiello M, Zito A, Ciccone M. Hypertensive Cardiomyopathy in Asymptomatic Patients: A Neglected Diagnosis. Curr Hypertens Rev. 2015 Apr 1;10(4):239–45.
31. Benson EA, Holdaway IM. Regulation of Insulin Binding to Human Mammary Carcinoma. Cancer Res. 1982 Mar 1;42(3):1137–41.
32. Milazzo G, Giorgino F, Damante G, Sung C, Stampfer MR, Vigneri R, et al. Insulin Receptor Expression and Function in Human Breast Cancer Cell Lines. Cancer Res [Internet]. 1992 [cited 2021 Jan 10];52(14):3924–30. Available from: https://pubmed.ncbi.nlm.nih.gov/1617668/
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36. McTernan PG, Anwar A, Eggo MC, Barnett AH, Stewart PM, Kumar S. Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue. Int J Obes [Internet]. 2000 [cited 2021 Jan 10];24(7):875–81. Available from: https://pubmed.ncbi.nlm.nih.gov/10918534/
37. Cauley JA, Gutai JP, Kuller LH, Ledonne D, Powell JG. The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol. 1989;129(6):1120–31.
38. 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 Aug 20;95(16):1218–26.
39. Baglietto L, English DR, Hopper JL, Morris HA, Tilley WD, Giles GG. Circulating insulin-like growth factor-I and binding protein-3 and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev [Internet]. 2007 Apr [cited 2021 Jan 10];16(4):763–8. Available from: https://pubmed.ncbi.nlm.nih.gov/17416768/
40. Rinaldi S, Peeters PHM, Berrino F, Dossus L, Biessy C, Olsen A, et al. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer [Internet]. 2006 Jun [cited 2021 Jan 10];13(2):593–605. Available from: https://pubmed.ncbi.nlm.nih.gov/16728585/
41. Rose DP, Haffner SM, Baillargeon J. Adiposity, the metabolic syndrome, and breast cancer in African-American and white American women [Internet]. Vol. 28, Endocrine Reviews. Endocr Rev; 2007 [cited 2021 Jan 10]. p. 763–77. Available from: https://pubmed.ncbi.nlm.nih.gov/17981890/
42. Chu MC, Cosper P, Orio F, Carmina E, Lobo RA. Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin. Am J Obstet Gynecol. 2006 Jan;194(1):100–4.
43. Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: Implications for the etiology of breast cancer. Breast Cancer Res. 2002;4(2):65–9.
44. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression [Internet]. Vol. 14, Endocrine-Related Cancer. Endocr Relat Cancer; 2007 [cited 2021 Jan 10]. p. 189–206. Available from: https://pubmed.ncbi.nlm.nih.gov/17639037/
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46. den Tonkelaar I, Seidell JC, Collette HJA. Body fat distribution in relation to breast cancer in women participating in the DOM-project. Breast Cancer Res Treat [Internet]. 1995 Apr [cited 2021 Jan 10];34(1):55–61. Available from: https://pubmed.ncbi.nlm.nih.gov/7749160/
47. Franceschi S, la Vecchia C, Negri E, Parazzini F, Boyle P. Breast cancer risk and history of selected medical conditions linked with female hormones. Eur J Cancer Clin Oncol [Internet]. 1990 [cited 2021 Jan 10];26(7):781–5. Available from: https://pubmed.ncbi.nlm.nih.gov/2145895/
48. de Waard F, Baanders‐Van Halewijn EA. A prospective study in general practice on breast‐cancer risk in postmenopausal women. Int J Cancer [Internet]. 1974 [cited 2021 Jan 10];14(2):153–60. Available from: https://pubmed.ncbi.nlm.nih.gov/4378317/
49. Moseson M, Koeni KL, Shor RE, Pasternac BS. The influence of medical conditions associated with hormones on the risk of breast cancer. Int J Epidemiol [Internet]. 1993 [cited 2021 Jan 10];22(6):1000–9. Available from: https://pubmed.ncbi.nlm.nih.gov/8144280/
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2. Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer [Internet]. Vol. 20, The Lancet Oncology. Lancet Publishing Group; 2019 [cited 2021 Jan 10]. p. e175–86. Available from: https://pubmed.ncbi.nlm.nih.gov/30842061/
3. Modi S, Saura C, Yamashita T, Park YH, Kim S-B, Tamura K, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610–21.
4. Barrios CH, Reinert T, Werutsky G. Global Breast Cancer Research: Moving Forward. Am Soc Clin Oncol Educ B [Internet]. 2018 May [cited 2021 Jan 10];38(38):441–50. Available from: https://pubmed.ncbi.nlm.nih.gov/30231347/
5. Harbeck N, Gnant M. Breast cancer [Internet]. Vol. 389, The Lancet. Lancet Publishing Group; 2017 [cited 2021 Jan 10]. p. 1134–50. Available from: https://pubmed.ncbi.nlm.nih.gov/27865536/
6. WHO Classification of Tumours of the Breast.
7. Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017 Jul 8;67(4):290–303.
8. Xue F, Michels KB. Diabetes, metabolic syndrome, and breast cancer: A review of the current evidence. In: American Journal of Clinical Nutrition [Internet]. American Society for Nutrition; 2007 [cited 2021 Jan 10]. Available from: https://pubmed.ncbi.nlm.nih.gov/18265476/
9. Vona-Davis L, Howard-Mcnatt M, Rose DP. Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer [Internet]. Vol. 8, Obesity Reviews. Obes Rev; 2007 [cited 2021 Jan 10]. p. 395–408. Available from: https://pubmed.ncbi.nlm.nih.gov/17716297/
10. Stoll BA, Secreto G. New hormone-related markers of high risk to breast cancer. Ann Oncol. 1992;3(6):435–8.
11. Lee AW, Tyrer JP, Doherty JA, Stram DA, Kupryjanczyk J, Dansonka-Mieszkowska A, et al. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study. Gynecol Oncol. 2015 Mar 1;136(3):542–8.
12. Mendonça FM, De Sousa FR, Barbosa AL, Martins SC, Araújo RL, Soares R, et al. Metabolic syndrome and risk of cancer: Which link? [Internet]. Vol. 64, Metabolism: Clinical and Experimental. W.B. Saunders; 2015 [cited 2021 Jan 10]. p. 182–9. Available from: https://pubmed.ncbi.nlm.nih.gov/25456095/
13. Fernandes JV, Cobucci RNO, Jatobá CAN, de Medeiros Fernandes TAA, de Azevedo JWV, de Araújo JMG. The Role of the Mediators of Inflammation in Cancer Development [Internet]. Vol. 21, Pathology and Oncology Research. Kluwer Academic Publishers; 2015 [cited 2021 Jan 10]. p. 527–34. Available from: https://pubmed.ncbi.nlm.nih.gov/25740073/
14. Schreier LE, Berg GA, Basilio FM, Lopez GI, Etkin AE, Wikinski RL. Lipoprotein alterations, abdominal fat distribution and breast cancer. Biochem Mol Biol Int [Internet]. 1999 [cited 2021 Jan 10];47(4):681–90. Available from: https://pubmed.ncbi.nlm.nih.gov/10319421/
15. Kang C, LeRoith D, Gallagher EJ. Diabetes, obesity, and breast cancer [Internet]. Vol. 159, Endocrinology. Oxford University Press; 2018 [cited 2021 Jan 10]. p. 3801–12. Available from: https://pubmed.ncbi.nlm.nih.gov/30215698/
16. Mathews L, Subramanya V, Zhao D, Ouyang P, Vaidya D, Guallar E, et al. Endogenous Sex Hormones and Endothelial Function in Postmenopausal Women and Men: The Multi-Ethnic Study of Atherosclerosis. J Womens Health (Larchmt). 2019 Jul 1;28(7):900–9.
17. Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med [Internet]. 1998 [cited 2021 Jan 10];15(7):539–53. Available from: https://pubmed.ncbi.nlm.nih.gov/9686693/
18. Targeting risk factors for reducing the racially disparate burden in breast cancer - PubMed [Internet]. [cited 2021 Jan 10]. Available from: https://pubmed.ncbi.nlm.nih.gov/30844741/
19. Fortner RT, Katzke V, Kühn T, Kaaks R. Obesity and breast cancer. In: Recent Results in Cancer Research [Internet]. Springer New York LLC; 2016 [cited 2021 Jan 10]. p. 43–65. Available from: https://pubmed.ncbi.nlm.nih.gov/27909901/
20. Bani IA, Williams CM, Boulter PS, Dickerson JWT. Plasma lipids and prolactin in patients with breast cancer. Br J Cancer. 1986;54(3):439–46.
21. Gaard M, Tretli S, Urdal P. Risk of breast cancer in relation to blood lipids: a prospective study of 31,209 Norwegian women. Cancer Causes Control [Internet]. 1994 Nov [cited 2021 Jan 10];5(6):501–9. Available from: https://pubmed.ncbi.nlm.nih.gov/7827236/
22. Lawlor DA, Smith GD, Ebrahim S. Hyperinsulinaemia and increased risk of breast cancer: Findings from the British women’s heart and health study. Cancer Causes Control [Internet]. 2004 Apr [cited 2021 Jan 10];15(3):267–75. Available from: https://pubmed.ncbi.nlm.nih.gov/15090721/
23. Muti P, Quattrin T, Grant BJB, Krogh V, Micheli A, Schünemann HJ, et al. Fasting glucose is a risk factor for breast cancer: A prospective study. Cancer Epidemiol Biomarkers Prev [Internet]. 2002 Nov 1 [cited 2021 Jan 10];11(11):1361–8. Available from: https://pubmed.ncbi.nlm.nih.gov/12433712/
24. Mink PJ, Shahar E, Rosamond WD, Alberg AJ, Folsom AR. Serum insulin and glucose levels and breast cancer incidence: The atherosclerosis risk in communities study. Am J Epidemiol. 2002 Aug 15;156(4):349–52.
25. Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001;45(3):S116–24.
26. Manjer J, Kaaks R, Riboli E, Berglund G. Risk of breast cancer in relation to anthropometry, blood pressure, blood lipids and glucose metabolism: A prospective study within the Malmö Preventive Project. Eur J Cancer Prev. 2001;10(1):33–42.
27. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8) [Internet]. Vol. 311, JAMA - Journal of the American Medical Association. American Medical Association; 2014 [cited 2021 Jan 10]. p. 507–20. Available from: https://pubmed.ncbi.nlm.nih.gov/24352797/
28. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings. Am J Cardiol [Internet]. 1986 Feb 15 [cited 2021 Jan 10];57(6):450–8. Available from: https://pubmed.ncbi.nlm.nih.gov/2936235/
29. Palmiero P, Zito A, Maiello M, Cameli M, Modesti PA, Muiesan ML, et al. Left Ventricular Diastolic Function in Hypertension: Methodological Considerations and Clinical Implications. J Clin Med Res [Internet]. 2015 [cited 2021 Jan 10];7(3):137–44. Available from: https://pubmed.ncbi.nlm.nih.gov/25584097/
30. Palmiero P, Maiello M, Zito A, Ciccone M. Hypertensive Cardiomyopathy in Asymptomatic Patients: A Neglected Diagnosis. Curr Hypertens Rev. 2015 Apr 1;10(4):239–45.
31. Benson EA, Holdaway IM. Regulation of Insulin Binding to Human Mammary Carcinoma. Cancer Res. 1982 Mar 1;42(3):1137–41.
32. Milazzo G, Giorgino F, Damante G, Sung C, Stampfer MR, Vigneri R, et al. Insulin Receptor Expression and Function in Human Breast Cancer Cell Lines. Cancer Res [Internet]. 1992 [cited 2021 Jan 10];52(14):3924–30. Available from: https://pubmed.ncbi.nlm.nih.gov/1617668/
33. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, et al. Fasting insulin and outcome in early-stage breast cancer: Results of a prospective cohort study. J Clin Oncol. 2002 Jan 1;20(1):42–51.
34. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease [Internet]. Vol. 20, Endocrine Reviews. Endocrine Society; 1999 [cited 2021 Jan 10]. p. 535–82. Available from: https://pubmed.ncbi.nlm.nih.gov/10453357/
35. Berrino F, Muti P, Micheli A, Bolelli G, Krogh V, Sciajno R, et al. Serum sex hormone levels after menopause and subsequent breast cancer. J Natl Cancer Inst. 1996 Mar 6;88(5):291–6.
36. McTernan PG, Anwar A, Eggo MC, Barnett AH, Stewart PM, Kumar S. Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue. Int J Obes [Internet]. 2000 [cited 2021 Jan 10];24(7):875–81. Available from: https://pubmed.ncbi.nlm.nih.gov/10918534/
37. Cauley JA, Gutai JP, Kuller LH, Ledonne D, Powell JG. The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol. 1989;129(6):1120–31.
38. 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 Aug 20;95(16):1218–26.
39. Baglietto L, English DR, Hopper JL, Morris HA, Tilley WD, Giles GG. Circulating insulin-like growth factor-I and binding protein-3 and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev [Internet]. 2007 Apr [cited 2021 Jan 10];16(4):763–8. Available from: https://pubmed.ncbi.nlm.nih.gov/17416768/
40. Rinaldi S, Peeters PHM, Berrino F, Dossus L, Biessy C, Olsen A, et al. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer [Internet]. 2006 Jun [cited 2021 Jan 10];13(2):593–605. Available from: https://pubmed.ncbi.nlm.nih.gov/16728585/
41. Rose DP, Haffner SM, Baillargeon J. Adiposity, the metabolic syndrome, and breast cancer in African-American and white American women [Internet]. Vol. 28, Endocrine Reviews. Endocr Rev; 2007 [cited 2021 Jan 10]. p. 763–77. Available from: https://pubmed.ncbi.nlm.nih.gov/17981890/
42. Chu MC, Cosper P, Orio F, Carmina E, Lobo RA. Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin. Am J Obstet Gynecol. 2006 Jan;194(1):100–4.
43. Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: Implications for the etiology of breast cancer. Breast Cancer Res. 2002;4(2):65–9.
44. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression [Internet]. Vol. 14, Endocrine-Related Cancer. Endocr Relat Cancer; 2007 [cited 2021 Jan 10]. p. 189–206. Available from: https://pubmed.ncbi.nlm.nih.gov/17639037/
45. Sonnenschein E, Toniolo P, Terry MB, Bruning PF, Kato I, Koenig KL, et al. Body fat distribution and obesity in pre- and postmenopausal breast cancer. Int J Epidemiol [Internet]. 1999 [cited 2021 Jan 10];28(6):1026–31. Available from: https://pubmed.ncbi.nlm.nih.gov/10661643/
46. den Tonkelaar I, Seidell JC, Collette HJA. Body fat distribution in relation to breast cancer in women participating in the DOM-project. Breast Cancer Res Treat [Internet]. 1995 Apr [cited 2021 Jan 10];34(1):55–61. Available from: https://pubmed.ncbi.nlm.nih.gov/7749160/
47. Franceschi S, la Vecchia C, Negri E, Parazzini F, Boyle P. Breast cancer risk and history of selected medical conditions linked with female hormones. Eur J Cancer Clin Oncol [Internet]. 1990 [cited 2021 Jan 10];26(7):781–5. Available from: https://pubmed.ncbi.nlm.nih.gov/2145895/
48. de Waard F, Baanders‐Van Halewijn EA. A prospective study in general practice on breast‐cancer risk in postmenopausal women. Int J Cancer [Internet]. 1974 [cited 2021 Jan 10];14(2):153–60. Available from: https://pubmed.ncbi.nlm.nih.gov/4378317/
49. Moseson M, Koeni KL, Shor RE, Pasternac BS. The influence of medical conditions associated with hormones on the risk of breast cancer. Int J Epidemiol [Internet]. 1993 [cited 2021 Jan 10];22(6):1000–9. Available from: https://pubmed.ncbi.nlm.nih.gov/8144280/
50. Agnoli C, Berrino F, Abagnato CA, Muti P, Panico S, Crosignani P, et al. Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: A nested case-control study. Nutr Metab Cardiovasc Dis [Internet]. 2010 Jan [cited 2021 Jan 10];20(1):41–8. Available from: https://pubmed.ncbi.nlm.nih.gov/19361966/
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02-09-2021
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Palmiero P, Maiello M, Cecere A, Ciccone MM. Metabolic syndrome and breast cancer: a dangerous association for postmenopausal women: A postmenopausal women prevention study . Acta Biomed [Internet]. 2021 Sep. 2 [cited 2024 Jul. 18];92(4):e2021177. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/11335
