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Pharmacological prevention methods in patients with cardiovascular disease with breast cancer – when, how, and for whom?
, 1, 1, 1, 1
Affiliations- 3rd Department of Cardiology, School of Medical Sciences in Zabrze, Medical University of Silesia, Zabrze, Poland
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Abstract
Breast cancer is the leading cause of cancer-related deaths in women worldwide. Patients with breast cancer are at an increased risk of cardiovascular toxicity, presently defined as cancer therapy-related cardiovascular toxicity (CTR-CVT). This article provides a summary of the current knowledge on pharmacological cardiovascular prevention in breast cancer patients. The ESC guidelines on cardio-oncology have defined CTR-CVT. Baseline risk stratification with widely accepted risk scores is essential to identify patients at higher risk of CTR-CVT. The guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARBs), and beta-blockers as preventive medications in high-risk patients. Clinical trials have shown ambiguous results for ACE-I/ARBs and beta-blockers in reducing cardiotoxicity, while co-administration of ACE-I/ARBs and beta-blockers did not show additional benefits in preventing cardiac dysfunction. Further research is needed to verify the efficacy of novel cardioprotective medication and optimize pharmacological strategies for cardiovascular prevention in breast cancer patients.
Abstract
Breast cancer is the leading cause of cancer-related deaths in women worldwide. Patients with breast cancer are at an increased risk of cardiovascular toxicity, presently defined as cancer therapy-related cardiovascular toxicity (CTR-CVT). This article provides a summary of the current knowledge on pharmacological cardiovascular prevention in breast cancer patients. The ESC guidelines on cardio-oncology have defined CTR-CVT. Baseline risk stratification with widely accepted risk scores is essential to identify patients at higher risk of CTR-CVT. The guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARBs), and beta-blockers as preventive medications in high-risk patients. Clinical trials have shown ambiguous results for ACE-I/ARBs and beta-blockers in reducing cardiotoxicity, while co-administration of ACE-I/ARBs and beta-blockers did not show additional benefits in preventing cardiac dysfunction. Further research is needed to verify the efficacy of novel cardioprotective medication and optimize pharmacological strategies for cardiovascular prevention in breast cancer patients.
Keywords
cardio-toxicity; cardiovascular prevention
About this articleTitle
Pharmacological prevention methods in patients with cardiovascular disease with breast cancer – when, how, and for whom?
Journal
Nowotwory. Journal of Oncology
Issue
Article type
Review paper
Published online
2023-08-21
Page views
43
Article views/downloads
17
DOI
Keywords
cardio-toxicity
cardiovascular prevention
Authors
Maciej Dyrbuś
Ilona Skoczylas
Aleksandra Majsnerowska
Mariusz Gąsior
Mateusz Tajstra
References (63)- American Cancer Society. Breast Cancer Facts & Figures 2022-2024. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2022-2024-breast-cancer-fact-figures-acs.pdf.
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–249.
- Ferlay J. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. 2020. https://gco.iarc.fr/today/home.
- Miklewska MJ, Klaudia B, Urszula W, et al. Morbidity and mortality trends of the most common cancers in 1990–2019. Poland’s position compared to other European countries. Nowotw J Oncol. 2023; 73(1): 46–55.
- Cherukuri SP, Chikatimalla R, Dasaradhan T, et al. Breast Cancer and the Cardiovascular Disease: A Narrative Review. Cureus. 2022; 14(8): e27917.
- Koric A, Chang CP, Mark B, et al. Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study. Cancer. 2022; 128(14): 2826–2835.
- Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022; 43(41): 4229–4361.
- Bobek-Billewicz B, Jurkowski M. The role of magnetic resonance imaging in the diagnosis of breast cancer. Nowotwory. Journal of Oncology. 2017; 67(3): 185–192.
- Perez IE, Taveras Alam S, Hernandez GA, et al. Cancer Therapy-Related Cardiac Dysfunction: An Overview for the Clinician. Clin Med Insights Cardiol. 2019; 13: 1179546819866445.
- Yeh E, Bickford C. Cardiovascular Complications of Cancer Therapy. J Am Coll Cardiol. 2009; 53(24): 2231–2247.
- Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA Cancer J Clin. 2016; 66(4): 309–325.
- Bowles EJ, Wellman R, Feigelson HS, et al. Pharmacovigilance Study Team. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012; 104(17): 1293–1305.
- Armenian SH, Xu L, Ky B, et al. Cardiovascular Disease Among Survivors of Adult-Onset Cancer: A Community-Based Retrospective Cohort Study. J Clin Oncol. 2016; 34(10): 1122–1130.
- Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of Anthracyclines. Front Cardiovasc Med. 2020; 7: 26.
- Santana BR, Codon JC, Olmos VJ, et al. HFA-ICOS cardiovascular toxicity risk score validation in CARDIOTOX registry. European Heart Journal. 2022; 43(Supplement_2).
- Tini G, Cuomo A, Battistoni A, et al. Baseline cardio-oncologic risk assessment in breast cancer women and occurrence of cardiovascular events: The HFA/ICOS risk tool in real-world practice. Int J Cardiol. 2022; 349: 134–137.
- Lyon AR, Dent S, Stanway S, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies : a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society. 2020.
- Visseren FLJ, Mach F, Smulders YM, et al. ESC National Cardiac Societies, ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021; 42(34): 3227–3337.
- Yamaguchi N, Fujii T, Aoi S, et al. Comparison of cardiac events associated with liposomal doxorubicin, epirubicin and doxorubicin in breast cancer: a Bayesian network meta-analysis. Eur J Cancer. 2015; 51(16): 2314–2320.
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42(36): 3599–3726.
- Gulati G, Heck S, Ree A, 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. 2016; 37(21): 1671–1680.
- Heck SL, Mecinaj A, Ree AH, et al. Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol. Circulation. 2021; 143(25): 2431–2440.
- Livi L, Barletta G, Martella F, et al. Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial. JAMA Oncol. 2021; 7(10): 1544–1549.
- Toko H, Oka T, Zou Y, et al. Angiotensin II type 1a receptor mediates doxorubicin-induced cardiomyopathy. Hypertens Res. 2002; 25(4): 597–603.
- Brilla CG, Rupp H, Maisch B. Effects of ACE inhibition versus non-ACE inhibitor antihypertensive treatment on myocardial fibrosis in patients with arterial hypertension. Retrospective analysis of 120 patients with left ventricular endomyocardial biopsies. Herz. 2003; 28(8): 744–753.
- Lou Q, Janardhan A, Efimov IR. Remodeling of calcium handling in human heart failure. Adv Exp Med Biol. 2012; 740: 1145–1174.
- Avila M, Ayub-Ferreira S, Wanderley Md, et al. Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity. J Am Coll Cardiol. 2018; 71(20): 2281–2290.
- Abreu RV, Santos DL, Moreno AJ. Effects of carvedilol and its analog BM-910228 on mitochondrial function and oxidative stress. J Pharmacol Exp Ther. 2000; 295(3): 1022–1030.
- Lueder Tv, Kotecha D, Atar D, et al. Neurohormonal Blockade in Heart Failure. Cardiac Failure Review. 2017; 03(01): 19.
- Bosch X, Rovira M, Sitges M, 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): 2355–2362.
- Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010; 376(9753): 1670–1681.
- Chotenimitkhun R, D'Agostino R, Lawrence JA, et al. Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function. Can J Cardiol. 2015; 31(3): 302–307.
- Sim Y, Lim C, Phyu N, et al. The Impact of Statin Use and Breast Cancer Recurrence - A Retrospective Study in Singapore. Front Oncol. 2022; 12: 835320.
- Van Wyhe RD, Rahal OM, Woodward WA. Effect of statins on breast cancer recurrence and mortality: a review. Breast Cancer (Dove Med Press). 2017; 9: 559–565.
- Casaburi I, Chimento A, De Luca A, et al. Cholesterol as an Endogenous ERRα Agonist: A New Perspective to Cancer Treatment. Front Endocrinol (Lausanne). 2018; 9: 525.
- Hundley WG, D'Agostino R, Crotts T, et al. Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment. NEJM Evid. 2022; 1(9).
- Clinicaltrials.gov Identifier: STOP-CA (Statins TO Prevent the Cardiotoxicity From Anthracyclines). https://clinicaltrials.gov/ct2/show/NCT02943590.
- Clinicaltrials.gov identifier: Statins for the Primary Prevention of Heart Failure in Patients Receiving Anthracycline Pilot Study (SPARE-HF). https://clinicaltrials.gov/ct2/show/NCT03186404.
- Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341(10): 709–717.
- Pitt B, Remme W, Zannad F, et al. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348(14): 1309–1321.
- Zannad F, Gattis Stough W, Rossignol P, et al. Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice. Eur Heart J. 2012; 33(22): 2782–2795.
- Akpek M, Ozdogru I, Sahin O, et al. Protective effects of spironolactone against anthracycline-induced cardiomyopathy. Eur J Heart Fail. 2015; 17(1): 81–89.
- Martín-Garcia A, López-Fernández T, Mitroi C, et al. Effectiveness of sacubitril-valsartan in cancer patients with heart failure. ESC Heart Fail. 2020; 7(2): 763–767.
- Gregorietti V, Fernandez TL, Costa D, et al. Use of Sacubitril/valsartan in patients with cardio toxicity and heart failure due to chemotherapy. Cardiooncology. 2020; 6(1): 24.
- Kanorskiy SG, Pavlovets VP. First experience of using valsartan/sacubitril in women with heart failure and breast cancer receiving anthracycline-based adjuvant chemotherapy. Medical Counc. 2019(16): 42–48.
- Clinicaltrials.gov identifier: Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM).
- Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015; 373(22): 2117–2128.
- McMurray JJ, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019; 381(21): 1995–2008.
- Joshi S, Singh T, Newby D, et al. Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure. Heart. 2021; 107(13): 1032–1038.
- Gongora CA, Drobni ZD, Quinaglia Araujo Costa Silva T, et al. Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines. JACC Heart Fail. 2022; 10(8): 559–567.
- Clinicaltrials.gov Identifier: Empagliflozin in the Prevention of Cardiotoxicity in Cancer Patients Undergoing Chemotherapy Based on Anthracyclines (EMPACT).
- Rock CL, Flatt SW, Newman V, et al. Factors associated with weight gain in women after diagnosis of breast cancer. Women's Healthy Eating and Living Study Group. J Am Diet Assoc. 1999; 99(10): 1212–1221.
- Irwin ML, Crumley D, McTiernan A, et al. Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer. 2003; 97(7): 1746–1757.
- Ma ZY, Yao SS, Shi YY, et al. Effect of aerobic exercise on cardiotoxic outcomes in women with breast cancer undergoing anthracycline or trastuzumab treatment: a systematic review and meta-analysis. Support Care Cancer. 2022; 30(12): 10323–10334.
- Tranchita E, Murri A, Grazioli E, et al. The Beneficial Role of Physical Exercise on Anthracyclines Induced Cardiotoxicity in Breast Cancer Patients. Cancers (Basel). 2022; 14(9).
- Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010; 42(7): 1409–1426.
- Curigliano G, Lenihan D, Fradley M, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020; 31(2): 171–190.
- Yang H, Bhoo-Pathy N, Brand JS, et al. Risk of heart disease following treatment for breast cancer - results from a population-based cohort study. Elife. 2022; 11.
- Bundred NJ. The effects of aromatase inhibitors on lipids and thrombosis. Br J Cancer. 2005; 93 Suppl 1(Suppl 1): S23–S27.
- Amir E, Seruga B, Niraula S, et al. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011; 103(17): 1299–1309.
- Hernandez RK, Sørensen HT, Pedersen L, et al. Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: a Danish population-based cohort study. Cancer. 2009; 115(19): 4442–4449.
- SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration, SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J. 2021; 42(25): 2439–2454.
- SCORE2-OP working group and ESC Cardiovascular risk collaboration. SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. Eur Heart J. 2021; 42(25): 2455–2467.