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Approccio endocrino metabolico - Dott. Andrea Laurenzi

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Approccio endocrino-metabolico alla paziente affetta da carcinoma mammario in blocco ormonale adiuvante: inquadramento diagnostico e trattamento della sindrome metabolica

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Approccio endocrino metabolico - Dott. Andrea Laurenzi

  1. 1. Approccio endocrino-metabolico alla paziente affetta da carcinoma mammario in blocco ormonale adiuvante: inquadramento diagnostico e trattamento della sindrome metabolica Andrea Laurenzi
  2. 2. agenda n Metabolic Syndrome n MetS and Breast Cancer Association n MetS as a risk factor for Breast Cancer n MetS as a consequence of BC treatment n MetS and Breast Cancer prognosis n Metabolic Syndrome Management n Diagnosis n Treatment
  3. 3. agenda n Metabolic Syndrome n Metabolic Syndrome and Breast Cancer n MS as a risk factor for BC n MS ad a consequence of BC treatment n MS and BC prognosis n Metabolic Syndrome Management n Diagnosis n Treatment
  4. 4. Samson SL, Garber AJ: Endocrinol Metab Clin N Am 2014 ≥ 102 cm in M ≥ 88 cm in F( ) metabolic syndrome
  5. 5. n Prevalence is age dependent (22- 43% in adults > 65 years, depending on population and on diagnostic criteria used) n It is not an absolute risk indicator n MetS presence, compared with its absence, is associated to: n 2-fold increase of CVD in the 10 years time n 5-fold increase of Type 2 Diabetes Beltran-Sanchez H et al., J Am Coll Cardiol 2013 Albert et al, Circulation 2009 epidemiology metabolic syndrome
  6. 6. Samson SL, Garber AJ: Endocrinol Metab Clin N Am 2014 physiology metabolic syndrome
  7. 7. agenda n Metabolic Syndrome n MetS and Breast Cancer n MetS as a risk factor for Breast Cancer n MetS as a consequence of BC treatment n MetS and Breast Cancer prognosis n Metabolic Syndrome Management n Diagnosis n Treatment
  8. 8. Bahndari R et Al, International Journal of Breast Cancer 2014 metabolic syndrome & breast cancer MetS: a risk factor for breast cancer
  9. 9. diabetes: a risk factor for breast cancer Larsson et Al, Int. J. Cancer 2007 metabolic syndrome & breast cancer
  10. 10. Gunter MJ et Al, Cancer Research 2015 IFG/IGT: a risk factor for breast cancer metabolic syndrome & breast cancer
  11. 11. IFG/IGT: a risk factor for breast cancer metabolic syndrome & breast cancer
  12. 12. agenda n Metabolic Syndrome n Metabolic Syndrome and Breast Cancer n MetS as a risk factor for Breast Cancer n MetS ad a consequence of BC treatment n MetS and Breast Cancer prognosis n Metabolic Syndrome Management n Diagnosis n Treatment
  13. 13. ER / PR / HER2 % of total BC Luminal-A + / + / – 67% Luminal-B + / + / + 15% Basal-like – / – / – 13% HER2-like – / – / + 5% breast cancer hormonal therapy Perou C et Al, Nature 2000 epidemiology
  14. 14. Xu et Al, Journal of Diabetes and Its Complications 2017 metabolic syndrome & breast cancer
  15. 15. Sun et Al, British Journal of Cancer 2014 tamoxifen and diabetes T2DM + 31% metabolic syndrome & breast cancer
  16. 16. short-term raloxifene and insulin sensitivity Nagamani et Al, Fertility an Sterility 2008 metabolic syndrome & breast cancer
  17. 17. long-term raloxifene and insulin sensitivity Lasco A et Al, Diabetologia 2004 metabolic syndrome & breast cancer
  18. 18. long-term raloxifene and LDL-C Dayspring T et Al, Metab Clin Exp 2006 metabolic syndrome & breast cancer
  19. 19. aromatase inhibitors and lipids after 3 months Bell et Al, J Clin Pharmacol 2013 n 503 women with post-menopausal breast cancer metabolic syndrome & breast cancer
  20. 20. agenda n Breast Cancer Hormonal Therapy n Metabolic Syndrome n Metabolic Syndrome and Breast Cancer n MetS as a risk factor for BC n MetS as a consequence of BC treatment n MetS and Breast Cancer prognosis n Metabolic Syndrome Management n Diagnosis n Treatment
  21. 21. Goodwin PJ et Al, J Clin Oncol 2002 hyperinsulinemia: a prognostic factor for BC metabolic syndrome & breast cancer
  22. 22. diabetes: a prognostic factor for BC Luo et Al, Breast Cancer Res Treat 2015 n 8108 women with invasive breast cancer metabolic syndrome & breast cancer
  23. 23. dyslipidemia: a prognostic factor for BC Li X et Al, Breast 2017 (≥ 115 mg/dL) (< 115 mg/dL) metabolic syndrome & breast cancer (≥ 40 mg/dL) (< 40 mg/dL)
  24. 24. take home messages n Obesity, diabetes, hyperinsulinemia, dyslipidemia are all risk factors for breast cancer n SERMs treatment is associate with: n worse outcome on diabetes compared to AIs n lipid panel: ↓ tot-C and LDL, mild ↑ of TG levels n Aromatase Inibhitors treatment correlates with: n better outcome on diabetes compared to SERMs n mild worsening of lipid panel (↓ HDL-C and ↑LDL-C) n Diabetes and lipids are also prognostic factors in term of all-causes mortality in breast cancer patients metabolic syndrome & breast cancer
  25. 25. agenda n Metabolic Syndrome n Metabolic Syndrome and Breast Cancer n MS as a risk factor for BC n MS as a consequence of BC treatment n MS and BC prognosis n Metabolic Syndrome Management n Diagnosis n Treatment
  26. 26. diagnosis metabolic syndrome management n Weight control n BMI n Abdominal circumference n Evaluate hyperinsulinemia n Fasting glycaemia n Basal insulin n Blood pressure n Lipid panel (Tot-C / HDL-C / TG) n Pharmacological anamnesis Glycemia (mg/dL) x Insulin (mU/L) ──────────────────────────── 405 HOMA-IR:
  27. 27. n The aim is to decrease risk of: n Cardio-Vascular Disease n Type 2 Diabetes n It involves: n implementation of lifestyle and dietary habits in order to loose weigth n treatment of IFG/IGT/diabetes n treatment of atherogenic dyslipidemia n treatment of hypertension treatment metabolic syndrome management
  28. 28. lifestyle intervention programs Yamaoka and Tango, BMC Medicine 2012 metabolic syndrome management
  29. 29. Insulino-sensibilizzanti - Biguanidi (metformina) - Glitazoni (pioglitazone) IGT/IFG/diabetes metabolic syndrome management Secretagoghi - Sulfaniluree (gliclazide, glimepiride, glibenclamide) - Glinidi (repaglinide) Incretine - GLP1 analoghi (liraglutide, lixisenatide, dulaglutide, exenatide LAR) - DPP-IV inibitori (sitagliptin, vildagliptin, alogliptin, linagliptin, saxagliption) Glicosurici - SGLT2 inibitori (dapagliflozin, empagliflozin, canagliflozin) Inibitore assorbimento intestinale del glucosio - Acarbosio
  30. 30. IGT/IFG/diabetes metabolic syndrome management ADA/EASD Position Statement 2012
  31. 31. 1) Lifestyle Interventions 2) Metformin IGT/IFG/diabetes metabolic syndrome management Inzucchi SE Et al, JAMA 2014
  32. 32. Coyle et Al, Annals of Oncology 2016 metabolic syndrome management IGT/IFG/diabetes
  33. 33. 3) d IGT/IFG/diabetes metabolic syndrome management SID/AMD Standard Italiani di Cura per il Diabete 2016
  34. 34. metabolic syndrome management IGT/IFG/diabetes Monami, Decembrini, Mannucci, ACTA Diab 2014
  35. 35. metabolic syndrome management IGT/IFG/diabetes n Tumor frequency and insulin dose positive correlation n After adjustment for insulin dose, authors reported HR 1.19, 95% CI 1.09-1.29 for glargine compared to NPH insulin n No significat HR for lispro or aspart insulins Hemkens et Al, Lancet 2009
  36. 36. metabolic syndrome management IGT/IFG/diabetes ORIGIN Study, N Eng J Med 2012
  37. 37. Friedewald’s formula (mg/dL): LDL= TC - HDL - TG/5 dyslipidemia metabolic syndrome management
  38. 38. dyslipidemia metabolic syndrome management
  39. 39. «Normal» (low risk) «Abnormal » (moderate risk) «Abnormal» (high risk) Total Col < 200 mg/dL 200-240 mg/dL > 240 mg/dL LDL-C < 130 mg/dL 130-160 mg/dL > 160 mg/dL HDL-C > 60 mg/dL 40-60 mg/dL < 40 mg/dL tryglicerides < 150 mg/dL 150-500 mg/dL > 500 mg/dL non-HDL C < 160 mg/dL 160-190 mg/dL > 190 mg/dL dyslipidemia metabolic syndrome management
  40. 40. Jacobson TA et Al. J Clin Lipidol 2014;8(5):477 metabolic syndrome management
  41. 41. dyslipidemia metabolic syndrome management Low Intensity Therapy Moderate Intensity Therapy High Intensity Therapy LDL reduction <30% LDL reduction 30-50% LDL reduction >50% Simva 20 mg Prava 10-20 mg Lova 10-20 mg Fluva 20-40 mg Atorva 10-20 mg Rosuva 5-10 mg Simva 20-40 mg Prava 40-80 mg Lova 40 mg Fluva 80 mg Atorva 40-80 mg Rosuva 20-40 mg à 40 mg/dL of LDL-C reduction correspons to –22% of CVDrisk
  42. 42. Ahern et Al, Lancet Oncology 2014 statin therapy and breast cancer recurrence metabolic syndrome management
  43. 43. dyslipidemia metabolic syndrome management n High dose anastrazole and letrozole are CYP1A2, CYP3A4 e CYP2C8/9 inhibitors, with consequent rosuvastatin metabolism reduction n Pravastatin is a mild CYP3A4 inductor, thus it can cause reduction of Aromatase Inhibitors levels
  44. 44. dyslipidemia: tryglycerides metabolic syndrome management n Normal level: < 150 mg/dL n Risk of acute pancreatitis if > 500 mg/dL 1) Omega 3 n Starting from 1g BID to 1 g TID 2) Fibrati (fenofibrate) n Fulcrosupra 145 mg
  45. 45. take home messages (2) n First step of MetS treatment is lifestyle improvement n When indicated, pharmacological therapy for diabetes must be tailored on patient characteristics n Consider Non-HDL as a better predictor for CVD in dislipidemic patients n Evaluate all risk factors to define target of dyslipidemia treatment metabolic syndrome management
  46. 46. Grazie!

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