Please confirm you are human (Sign Up for free to never see this)
← Back to Search
Cardiotoxicity Associated With Cancer Therapy: Pathophysiology And Prevention
R. Adão, G. D. Keulenaer, A. Leite-Moreira, C. Brás-Silva
Published 2013 · Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Cardiotoxicity is one of the most significant adverse effects of cancer treatment, and is responsible for considerable morbidity and mortality. Among the effects of chemothera- peutic agents on the cardiovascular system, the most frequent and serious is heart failure with ventricular systolic dysfunction. Other toxic effects include hypertension, thromboembolic dis- ease, pericardial disease, arrhythmias and myocardial ischemia. For several decades, cancer therapy-induced cardiomyopathy was almost exclusively associated with the use of cumulative doses of anthracyclines, which cause permanent damage at the cellular level. However, new therapeutic agents, such as the monoclonal antibody trastuzumab, induce transient reversible myocyte dysfunction which is unrelated to the dose used. Early identification of potential car- diovascular injury, accurate diagnosis of cardiotoxic events and implementation of appropriate monitoring plans are essential in patients with cancer. Close cooperation between cardiologists and oncologists is thus crucial, in order to balance the risks and benefits of cardiotoxic anti- cancer therapy. In this article we review the various responses to cardiotoxic cancer treatments and their relationship with the main antineoplastic drugs used in clinical practice. In addition, we discuss the main guidelines on detection and monitoring of cardiotoxicity in patients with cancer.
This paper references
Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy.
H. Burris (2011)
Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer.
M. Ryberg (1998)
Role of anthracyclines in the era of targeted therapy
H. Cortés-Funés (2007)
Prodrugs of anthracyclines in cancer chemotherapy.
F. Kratz (2006)
Activation of AMPactivated protein kinase by human EGF receptor 2/EGF 408 R. Adão et al. receptor tyrosine kinase inhibitor protects cardiac cells
NL Spector (2007)
Estimates of cancer incidence and mortality in Europe in 1995.
F. Bray (2002)
Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells
N. Spector (2007)
Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
M. Onaitis (2010)
Risk of thrombosis with lenalidomide and its prevention with aspirin.
J. Hirsh (2007)
Unlocking the mysteries of diastolic function: deciphering the Rosetta Stone 10 years later.
S. Lester (2008)
Type 1 receptor tyrosine kinase profiles identify patients with enhanced benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial.
J. Bartlett (2008)
Mechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection?
D. Sawyer (2010)
Cardiac dysfunction in the trastuzumab clinical trials experience.
A. Seidman (2002)
Cardiovascular side-effects of modern cancer therapy.
M. Minami (2010)
XeNA: Capecitabine Plus Docetaxel, With or Without Trastuzumab, as Preoperative Therapy for Early Breast Cancer
Stefan Glück (2008)
Targeted cancer therapy: conferring specificity to cytotoxic drugs.
R. Chari (2008)
Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study.
L. Kremer (2001)
Effects of in vitro and in vivo exposure to doxorubicin (adriamycin) on caffeine-induced Ca2+ release from sarcoplasmic reticulum and contractile protein function in 'chemically-skinned' rabbit ventricular trabeculae.
S. Takahashi (1998)
ACC / AHA
JL Anderson (2007)
Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy.
S. Swain (1997)
A woman's heart
M. Ewer (2009)
Cardiovascular toxicity caused by cancer treatment: strategies for early detection.
R. Altena (2009)
The liposomal formulation of doxorubicin.
S. Abraham (2005)
Antioxidants and cancer therapy: a systematic review.
E. Ladas (2004)
TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer
K. Villman (2006)
Doxorubicin cardiotoxicity: analysis of prevailing hypotheses
R. Olson (1990)
NADPH oxidase-derived superoxide anion mediates angiotensin II-induced cardiac hypertrophy.
H. Nakagami (2003)
Heart to heart with trastuzumab: a review on cardiac toxicity
S. Cosimo (2011)
Activation of AMPK is necessary for killing cancer cells and sparing cardiac cells
Scott A. Shell (2008)
Adult multicenter trials using dexrazoxane to protect against cardiac toxicity.
S. Swain (1998)
Predicting and preventing cardiotoxicity in the era of breast cancer targeted therapies. Novel molecular tools for clinical issues.
A. Zambelli (2011)
Neuregulins Promote Survival and Growth of Cardiac Myocytes
Y. Zhao (1998)
Cardiotoxicity of Anticancer Drugs: The Need for Cardio-Oncology and Cardio-Oncological Prevention
A. Albini (2010)
Estimates of cancer incidence and mortality in Europe in 2008.
J. Ferlay (2010)
Parenteral administration of recombinant human neuregulin‐1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses
A. Jabbour (2011)
Cardiotoxicidad por 5-fluorouracilo: ¿isquemia o toxicidad miocárdica?
F. L. Medrano (2001)
Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma
G. Hortobagyi (1989)
HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil.
A. Di Leo (2002)
Targeting HER2positive breast cancer with trastuzumab-DM1, an antibodycytotoxic drug conjugate
GD Lewis Phillips (2008)
Role of Neuregulin-1/ErbB Signaling in Cardiovascular Physiology and Disease: Implications for Therapy of Heart Failure
K. Lemmens (2007)
Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy
C. Özcelik (2002)
Thalidomide and thrombosis.
P. Mehta (2003)
Cardiotoxicity of anticancer treatments: what the cardiologist needs to know
M. Ewer (2010)
Idarubicin (4demethoxydaunorubicin). A preliminary overview of preclinical and clinical studies
F Ganzina (1986)
Management of hypertension in angiogenesis inhibitor-treated patients.
H. Izzedine (2009)
Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management.
E. T. Yeh (2004)
update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the
L M Schuchter (2002)
Anthracyclineinduced clinical heart failure in a cohort of 607 children: long-term follow-up study
LC Kremer (2001)
Cardiotoxicity associated with cancer therapy: pathophysiology and prevention strategies.
R. Adão (2013)
c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.
H. Muss (1994)
Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity.
M. Ewer (2005)
Trastuzumab-induced cardiac dysfunction: A 'dual-hit'.
Matthew R. Zeglinski (2011)
Role of neuregulin1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure
K Lemmens (2007)
Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors.
C. Serrano (2012)
Properties of G-protein modulated receptor-adenylyl cyclase system in myocardium of spontaneously hypertensive rats treated with adriamycin.
M. Fu (1994)
Trastuzumabrelated cardiotoxicity in the elderly: a role for cardiovascular risk factors
C Serrano (2011)
Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.
H. Joensuu (2006)
Different anthracycline derivates for reducing cardiotoxicity in cancer patients.
E. C. van Dalen (2006)
A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine.
C. Myers (1983)
Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study
C. Kosmas (2007)
Monitoring for Cardiovascular Disease in Survivors of Childhood Cancer: Report From the Cardiovascular Disease Task Force of the Children's Oncology Group
S. Shankar (2008)
Anthracycline-Associated Cardiotoxicity in Survivors of Childhood Cancer
B. Trachtenberg (2010)
Hudson et al.
E. Anderson (1977)
Radiation-Induced Heart Disease: A Clinical Update
S. Yusuf (2011)
ErbB2 is essential in the prevention of dilated cardiomyopathy
S. Crone (2002)
Neoplastic pericardial disease: Old and current strategies for diagnosis and management.
C. Lestuzzi (2010)
Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.
M. Ewer (2005)
Ongoing phase I and II studies of novel anthracyclines
C. Sessa (2007)
Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate.
Gail D Lewis Phillips (2008)
Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy
A. Khorana (2007)
Preclinical assessment of cardiac toxicity.
R. Kettenhofen (2008)
Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab.
M. Scartozzi (2009)
New developments in anthracycline-induced cardiotoxicity.
A. Mordente (2009)
[Cardiotoxicity of 5-fluorouracil: ischemia or myocardial toxicity?].
F. López Medrano (2001)
Anthracyclineassociated cardiotoxicity in survivors of childhood cancer
BH Trachtenberg (2011)
Factors affecting late mortality from heart disease after treatment of Hodgkin's disease.
S. Hancock (1993)
Serum HER2 levels are increased in patients with chronic heart failure
Patrick J. Perik (2007)
Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology
T. Eschenhagen (2011)
2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology.
L. Schuchter (2002)
Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases.
J. Veinot (1996)
Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
C. Geyer (2006)
Molecular Mechanisms of Doxorubicin-induced Cardiomyopathy
R. Jeyaseelan (1997)
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
M. Piccart-Gebhart (2005)
Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model.
D. Dodd (1993)
Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations.
M. Martín (2009)
[Cost of cancer care in Portugal].
A. Araújo (2009)
update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology
LM Schuchter (2002)
Prolongation of the QT Interval and Ventricular Tachycardia in Patients Treated with Arsenic Trioxide for Acute Promyelocytic Leukemia
K. Ohnishi (2000)
F. Ganzina (2004)
Anticancer drugs and cardiotoxicity: Insights and perspectives in the era of targeted therapy.
E. Raschi (2010)
Anthracyclines Induce Calpain-dependent Titin Proteolysis and Necrosis in Cardiomyocytes*
C. Lim (2004)
New insights on signaling cascades induced by cross-talk between angiotensin II and aldosterone
C. Lemarié (2008)
Prevention of High-Dose Chemotherapy-Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition
D. Cardinale (2006)
Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility.
M. Telli (2007)
Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab.
F. Scappaticci (2007)
Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.
E. T. Yeh (2009)
4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data.
F. Ganzina (1983)
Liposomal drug formulations in cancer therapy: 15 years along the road.
M. Slingerland (2012)
Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer.
N. Robert (2006)
The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma
S. Deitcher (2004)
Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin).
M. Sliwkowski (1999)
A preliminary overview of preclinical and clinical studies
F Ganzina (1986)
Estimates of the cancer incidence and mortality in Europe in 2006.
J. Ferlay (2007)
Adjuvant therapy for HER2 positive breast cancer: are anthracyclines still necessary?
A. Castrellon (2008)
A clinicopathologic analysis of adriamycin cardiotoxicity
E. Lefrak (1973)
Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia.
S. Lipshultz (2005)
Zebrafish: an emerging technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug discovery
T. Barros (2008)
Cardio-oncology in targeting the HER receptor family: the puzzle of different cardiotoxicities of HER2 inhibitors.
A. Albini (2011)
Tissue‐specific mtDNA lesions and radical‐associated mitochondrial dysfunction in human hearts exposed to doxorubicin
D. Lebrecht (2005)
Anthracycline Cardiomyopathy Is Mediated by Depletion of the Cardiac Stem Cell Pool and Is Rescued by Restoration of Progenitor Cell Function
A. De Angelis (2010)
Introducing a new entity: chemotherapy-induced arrhythmia.
M. Guglin (2009)
Cardiovascular toxicity associated with cancer treatment.
P. Viale (2008)
Requirement for neuregulin receptor erbB2 in neural and cardiac development
Kuo-Fen Lee (1995)
Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro.
H. Ito (1990)
Protecting against anthracycline‐induced myocardial damage: a review of the most promising strategies
Karlijn A Wouters (2005)
This paper is referenced by
Significance of Echocardiography in the Assessment of Left Ventricular Function in Patients Receiving Combined Adjuvant Treatment with Anthracyclines and Trastuzumab / Značaj ehokardiografije u proceni funkcije leve komore kod bolesnica na adjuvantnoj terapji (kombinovana terapija antraciklinima i t
Ivana Ilić Krstić (2015)
Cardiotoxicity and Cardioprotection in Childhood Cancer
S. Lipshultz (2014)
From the Cover: Investigative Nonclinical Cardiovascular Safety and Toxicology Studies with BMS-986094, an NS5b RNA-Dependent RNA Polymerase Inhibitor
M. Gill (2017)
Experimental study of radiogenic heart damage using in vitro and in vivo animal models
Kiscsatári Laura (2016)
Block ionomer micellar nanoparticles from double hydrophilic copolymers, classifications and promises for delivery of cancer chemotherapeutics
Samirasadat Abolmaali (2017)
Early Myocardial Injury in Children on Cancer Chemotherapy
Esther W Kimani (2017)
Powikłania kardiologiczne u pacjentek z niezaawansowanym rakiem piersi po leczeniu uzupełniającym trastuzumabem
Kufel-Grabowska Joanna (2015)
Cardiovascular Complications of Chemotherapy
Mohamed Elazazy (2019)
Analysis of the intricate relationship between chronic inflammation and cancer.
Edna Zhi Pei Chai (2015)
Evaluación ecocardiográfica de la función ventricular derecha para la detección temprana de la cardiotoxicidad inducida por antraciclinas
Jenny Karina Villasmil Camacho (2017)
Intraventricular pressure gradients in heart failure.
M. Guerra (2013)
Unanticipated Cardiotoxicity Associated with Targeted Anticancer Therapy in Patients with Hematologic Malignancies Patients: Natural History and Risk Factors
Chintan P Shah (2017)
Cucurbitacin-I induces hypertrophy in H9c2 cardiomyoblasts through activation of autophagy via MEK/ERK1/2 signaling pathway.
Y. Wu (2016)
Inhibition of cancer antioxidant defense by natural compounds
A. Sznarkowska (2017)
Protective effect of silymarin against chemical-induced cardiotoxicity
B. M. Razavi (2016)
Late Cardiotoxicity: Issues for Childhood Cancer Survivors
Jyothsna Akam-Venkata (2016)
Drug Induced Cardiotoxicity: Mechanism, Prevention and Management
M. Kelleni (2018)
Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity
Raphaëlle Corremans (2019)