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Risk of Cardiomyopathy in Breast Cancer: How Can We Attenuate the Risk of Heart Failure from Anthracyclines and Anti-HER2 Therapies?

  • Cardio-oncology (M Fradley, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

To review cardiotoxicity of and strategies to prevent cardiotoxicity from anthracyclines and anti-HER2 agents used to treat breast cancer.

Recent findings

Although not common, cardiotoxicity from anthracyclines and anti-HER2 therapies is a major consideration in the use of these agents, especially in the adjuvant setting. Modifications in anthracycline agent, dosing, or schedule or use of Dexrazoxane have been shown to ameliorate the mostly irreversible cardiotoxicity from anthracyclines. Dose delays have been the primary means of addressing the possibly reversible cardiotoxicity from the anti-HER2 agent, trastuzumab, whereas the other anti-HER2 therapies, pertuzumab, lapatinib, and neratinib, are relatively nontoxic to the myocardium. Data from recent randomized clinical trials suggest that the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), and beta blockers may prevent subclinical cardiotoxicity, as measured by decline in the left ventricular ejection fraction, associated with these agents. Longer-term follow-up will be needed to confirm their role in prevention of symptomatic cardiomyopathy and subsequent cardiovascular disease in women with breast cancer.

Summary

Preliminary evidence suggests that the use of ACEi, ARB, and beta blockers during treatment with anthracyclines and trastuzumab may prevent subsequent cardiomyopathy. Larger trials with meaningful clinical endpoints are needed.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.

    Article  PubMed  Google Scholar 

  2. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300.

    Article  CAS  PubMed  Google Scholar 

  3. Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res. 2011;13(3):R64.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shenoy C, Klem I, Crowley AL, Patel MR, Winchester MA, Owusu C, et al. Cardiovascular complications of breast cancer therapy in older adults. Oncologist. 2011;16(8):1138–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther. 2017;31(1):63–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Groarke JD, Nohria A. Anthracycline cardiotoxicity: a new paradigm for an old classic. Circulation. 2015;131(22):1946–9.

    Article  PubMed  Google Scholar 

  7. Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10.

  8. Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc. 2014;3(2):e000665.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, et al. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007;67(18):8839–46.

    Article  CAS  PubMed  Google Scholar 

  10. Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24):2231–47.

    Article  CAS  PubMed  Google Scholar 

  11. Wojnowski L, Kulle B, Schirmer M, Schluter G, Schmidt A, Rosenberger A, et al. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation. 2005;112(24):3754–62.

    Article  CAS  PubMed  Google Scholar 

  12. Wang L, Tan TC, Halpern EF, Neilan TG, Francis SA, Picard MH, et al. Major cardiac events and the value of echocardiographic evaluation in patients receiving anthracycline-based chemotherapy. Am J Cardiol. 2015;116(3):442–6.

    Article  CAS  PubMed  Google Scholar 

  13. Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981–8.

    Article  CAS  PubMed  Google Scholar 

  14. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91(5):710–7.

    Article  Google Scholar 

  15. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79.

    Article  CAS  PubMed  Google Scholar 

  16. Qin A, Thompson CL, Silverman P. Predictors of late-onset heart failure in breast cancer patients treated with doxorubicin. J Cancer Surviv. 2015;9(2):252–9.

    Article  PubMed  Google Scholar 

  17. Legha SS, Benjamin RS, Mackay B, Ewer M, Wallace S, Valdivieso M, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med. 1982;96(2):133–9.

    Article  CAS  PubMed  Google Scholar 

  18. Batist G. Cardiac safety of liposomal anthracyclines. Cardiovasc Toxicol. 2007;7(2):72–4.

    Article  CAS  PubMed  Google Scholar 

  19. Hasinoff BB, Herman EH. Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol. 2007;7(2):140–4.

    Article  CAS  PubMed  Google Scholar 

  20. Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol. 2007;25(5):493–500.

    Article  CAS  PubMed  Google Scholar 

  21. Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997;15(4):1318–32.

    Article  CAS  PubMed  Google Scholar 

  22. Salzer WL, Devidas M, Carroll WL, Winick N, Pullen J, Hunger SP, et al. Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984-2001: a report from the children's oncology group. Leukemia. 2010;24(2):355–70.

    Article  CAS  PubMed  Google Scholar 

  23. Vrooman LM, Neuberg DS, Stevenson KE, Asselin BL, Athale UH, Clavell L, et al. The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL consortium. Eur J Cancer. 2011;47(9):1373–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229.

    Article  CAS  PubMed  Google Scholar 

  25. Landmesser U, Bahlmann F, Mueller M, Spiekermann S, Kirchhoff N, Schulz S, et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation. 2005;111(18):2356–63.

    Article  CAS  PubMed  Google Scholar 

  26. Riad A, Du J, Stiehl S, Westermann D, Mohr Z, Sobirey M, et al. Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. Eur J Pharmacol. 2007;569(3):204–11.

    Article  CAS  PubMed  Google Scholar 

  27. Henninger C, Fritz G. Statins in anthracycline-induced cardiotoxicity: Rac and rho, and the heartbreakers. Cell Death Dis. 2017;8(1):e2564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Riad A, Bien S, Westermann D, Becher PM, Loya K, Landmesser U, et al. Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice. Cancer Res. 2009;69(2):695–9.

    Article  CAS  PubMed  Google Scholar 

  29. Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012;60(23):2384–90.

    Article  CAS  PubMed  Google Scholar 

  30. Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer. 2013;49(13):2900–9.

    Article  CAS  PubMed  Google Scholar 

  31. Georgakopoulos P, Roussou P, Matsakas E, Karavidas A, Anagnostopoulos N, Marinakis T, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol. 2010;85(11):894–6.

    Article  CAS  PubMed  Google Scholar 

  32. Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006;48(11):2258–62.

    Article  CAS  PubMed  Google Scholar 

  33. Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013;167(5):2306–10.

    Article  PubMed  Google Scholar 

  34. Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of malignant hEmopathies). J Am Coll Cardiol. 2013;61(23):2355–62.

    Article  CAS  PubMed  Google Scholar 

  35. Yun S, Vincelette ND, Abraham I. Cardioprotective role of beta-blockers and angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a systematic review and meta-analysis. Postgrad Med J. 2015;91(1081):627–33.

    Article  CAS  PubMed  Google Scholar 

  36. Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114(23):2474–81.

    Article  CAS  PubMed  Google Scholar 

  37. Dessi M, Madeddu C, Piras A, Cadeddu C, Antoni G, Mercuro G, et al. Long-term, up to 18 months, protective effects of the angiotensin II receptor blocker telmisartan on Epirubin-induced inflammation and oxidative stress assessed by serial strain rate. SpringerPlus. 2013;2(1):198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. • Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37(21):1671–80 The PRADA study was a 2 x 2 factorial, randomized, placebo-controlled, double-blind, single center trial designed to compare the use of (i) the ARB candesartan, (ii) the betablocker metoprolol succinate, (iii) both candesartan and metoprolol, or (iv) matching placebos in preventing decline in left ventricular ejection fraction (LVEF) among women receiving adjuvant anthracycline (and trastuzumab if the cancer was HER2 positive). No patient developed heart failure. Patients receiving candesartan had modest, but statistically significant, smaller decline in LVEF.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. • Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR Jr, das Dores Cruz F, Goncalves Brandao SM, Rigaud VOC, et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY Trial. J Am Coll Cardiol. 2018;71(20):2281–90 The CECCY study was a randomized study of carvedilol versus placebo in women with early stage, HER2 negative, breast cancer where adjuvant anthracycline therapy was used. The study showed no difference in changes in LVEF or BNP levels between carvedilol and placebo-treated groups, but there was a lower incidence of diastolic dysfunction and less troponin I elevations were seen in the carvedilol group.

    Article  CAS  PubMed  Google Scholar 

  40. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22):1651–8.

    Article  CAS  PubMed  Google Scholar 

  41. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999;353(9169):2001–7.

  42. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9–13.

  43. Beta-Blocker Evaluation of Survival Trial I, Eichhorn EJ, Domanski MJ, Krause-Steinrauf H, Bristow MR, Lavori PW. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001;344(22):1659–67.

    Article  Google Scholar 

  44. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.

    Article  CAS  PubMed  Google Scholar 

  45. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28(1):92–8.

    Article  CAS  PubMed  Google Scholar 

  46. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

    Article  CAS  PubMed  Google Scholar 

  47. Meisel JL, Venur VA, Gnant M, Carey L. Evolution of targeted therapy in breast cancer: where precision medicine began. American Society of Clinical Oncology educational book/ASCO American Society of Clinical Oncology Meeting. 2018;(38):78–86.

  48. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011;9(1):16–32.

    Article  PubMed  CAS  Google Scholar 

  49. Ponde NF, Lambertini M, de Azambuja E. Twenty years of anti-HER2 therapy-associated cardiotoxicity. ESMO Open. 2016;1(4):e000073.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215–21.

    Article  CAS  PubMed  Google Scholar 

  51. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375(9712):377–84.

    Article  CAS  PubMed  Google Scholar 

  52. Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23(16):3676–85.

    Article  CAS  PubMed  Google Scholar 

  53. Spielmann M, Roche H, Delozier T, Canon JL, Romieu G, Bourgeois H, et al. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol. 2009;27(36):6129–34.

    Article  CAS  PubMed  Google Scholar 

  54. Viani GA, Afonso SL, Stefano EJ, De Fendi LI, Soares FV. Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer. 2007;7:153.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.

    Article  CAS  PubMed  Google Scholar 

  56. Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23(31):7811–9.

    Article  CAS  PubMed  Google Scholar 

  57. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72.

    Article  CAS  PubMed  Google Scholar 

  59. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354(8):809–20.

    Article  CAS  PubMed  Google Scholar 

  60. Ewer SM, Ewer MS. Cardiotoxicity profile of trastuzumab. Drug Saf. 2008;31(6):459–67.

    Article  CAS  PubMed  Google Scholar 

  61. Smith I, Procter M, Gelber DR, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369(9555):29–36.

    Article  CAS  PubMed  Google Scholar 

  62. Procter M, Suter TM, de Azambuja E, Dafni U, van Dooren V, Muehlbauer S, et al. Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin adjuvant (HERA) trial. J Clin Oncol. 2010;28(21):3422–8.

    Article  PubMed  Google Scholar 

  63. Romond EH, Jeong JH, Rastogi P, Swain SM, Geyer CE Jr, Ewer MS, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30(31):3792–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Serrano C, Cortes J, De Mattos-Arruda L, Bellet M, Gomez P, Saura C, et al. Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol. 2012;23(4):897–902.

    Article  CAS  PubMed  Google Scholar 

  65. Perez EA, Suman VJ, Davidson NE, Kaufman PA, Martino S, Dakhil SR, et al. Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. J Clin Oncol. 2004;22(18):3700–4.

    Article  CAS  PubMed  Google Scholar 

  66. Guarneri V, Lenihan DJ, Valero V, Durand JB, Broglio K, Hess KR, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006;24(25):4107–15.

    Article  CAS  PubMed  Google Scholar 

  67. Tripathy D, Seidman A, Keefe D, Hudis C, Paton V, Lieberman G. Effect of cardiac dysfunction on treatment outcomes in women receiving trastuzumab for HER2-overexpressing metastatic breast cancer. Clin Breast Cancer. 2004;5(4):293–8.

    Article  CAS  PubMed  Google Scholar 

  68. Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104(17):1293–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2014;15(10):1063–93.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Fox KF. The evaluation of left ventricular function for patients being considered for, or receiving Trastuzumab (Herceptin) therapy. Br J Cancer. 2006;95(10):1454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Khouri MG, Klem I, Shenoy C, Sulpher J, Dent SF. Screening and monitoring for cardiotoxicity during Cancer treatment. In: Kimmick GG, Lenihan DJ, Sawyer DB, Mayer EL, Hershman DL, editors. Cardio-Oncology: The Clinical Overlap of Cancer and Heart Disease. Switzerland: Springer; 2017. p. 43–80.

    Chapter  Google Scholar 

  72. • Pituskin E, Mackey JR, Koshman S, Jassal D, Pitz M, Haykowsky MJ, et al. Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101-Breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J Clin Oncol. 2017;35(8):870–7 The Multidisciplinary Approach to Novel Therapies in Cardio Oncology Research (MANTICORE) trial was a randomized prospective trial to compare placebo versus the ACEi perindopril versus the selective beta1-blocker bisoprolol in women receiving adjuvant trastuzumab. In multivariate analysis, baseline idex LV end-diastolic volume (LVEDVi) was predictive of change in LVEDVi, decline in LVEF was predicted by baseline LVEF, and perindopril and bisoprolol were independent predictors of maintained LVEF. Both perindopril and bisoprolol, therefore, protected against LVEF decline, but neither significantly affected LV remodeling.

    Article  CAS  PubMed  Google Scholar 

  73. Munster P, Krischer J, Tamura K, Bello-Matricaria L, Fink A, McCaskill-Stevens W, et al. Randomized trial of lisinopril or carvedilol for the prevention of cardiotoxicity in patients with early stage HER2-positive breast cancer receiving adjuvant trastuzumab. Ann Oncol. 2018;29(suppl_8):viii58–86.

    Article  Google Scholar 

  74. Munster P, Krischer J, Tamura R, Fink A, Bello-Matricaria L, Guilin M. A randomized community-based trial of an angiotensin-converting enzyme inhibitor, lisinopril or a beta blocker, carvedilol for the prevention of cardiotoxicity in patients with early stage HER2-positive breast cancer receiving adjuvant trastuzumab. Cancer Research. 2018 (Oral presentation at: 2018 San Antonio Breast Cancer Symposium; December 4–8, 2018; San Antonio, TX.): Abstract GS5-01.

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  1. Medical Oncology, Duke Cancer Institute / Duke University Medical Center, Box 3204 DUMC, Durham, NC, 27710, USA

    Gretchen Kimmick MD, MS & Susan Dent MD

  2. Cardiology, Duke University Medical Center, Durham, NC, USA

    Igor Klem MD

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Correspondence to Gretchen Kimmick MD, MS.

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Gretchen Kimmick is on the Scientific Advisory Boards of Boehringer Ingelheim; Eisai [Epirubicin]; Genomic Health [OncotypeDX]; and Agendia [MammaPrint]; consulting/advising relationship with Genomic Health, AstraZeneca, Novartis, Pfizer; received Honoraria (speakers bureau) from Eisai; and Research Funding: Bionovo, PUMA, and Roche. Dr. Kimmick and group have participated, current and in past, in research funded by the following: Abbott Laboratories, AbbVie, Abraxis BioScience, Alphavax, AstraZeneca, Bionovo, BiPar Sciences, Bristol-Meyers Squibb, Celldex Therapeutics, Celsion, EMD Serono, Exelixis, Genentech, GlaxoSmithKline (CARG Trial), Incyte Corporation, Janssen, Johnson & Johnson Pharmaceuticals, Medimmune, Merck, Merrimack Pharmaceuticals, Mylan Pharmaceuticals, Myriad Genetics, Nektar Therapeutics, NRG Oncology, Novartis, Pfizer, Pharmacyclics, Roche Pharmaceuticals, Roxane Laboratories, Sanofi, Veridex LLC, and Wyeth.

Susan Dent is on the advisory board for Hoffman La-Roche.

Igor Klem declares no potential conflicts of interest.

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Kimmick, G., Dent, S. & Klem, I. Risk of Cardiomyopathy in Breast Cancer: How Can We Attenuate the Risk of Heart Failure from Anthracyclines and Anti-HER2 Therapies?. Curr Treat Options Cardio Med 21, 30 (2019). https://doi.org/10.1007/s11936-019-0736-1

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