US Pharm. 2014;39(2):HS2-HS10.
ABSTRACT: Great advances have been made in the arena of cancer
drug therapy. A number of modalities, such as targeted therapies, have
emerged that have drastically changed the clinical landscape of
cancer-related drug therapy. The advent of these various targeted
therapies, however, has increased the incidence of
cardiotoxicity-related events in cancer patients. It is crucial that
cardiotoxicity in cancer patients be managed effectively by the
healthcare practitioner in order to decrease the mortality and morbidity
associated with the underlying malignancy.
The goals of cancer drug therapy are to cure the disease, prevent
disease recurrence, and decrease mortality. More cancer patients are
surviving because of advances in cancer-related drug therapies.
Cardiotoxicity, in which the heart muscle is damaged and cannot
efficiently pump blood to oxygenate the body’s vital organs, is one of
the most prominent morbidities in cancer patients surviving 5 to 10
years post therapy. Cardiotoxicity may lead to increased mortality and
disease progression because the therapeutic options are suboptimal.1,2
There are many deficits in scientific knowledge concerning cancer
therapy–induced cardiotoxicity, including the area of basic clinical
science. Such deficits encumber progress in this area. Major
cancer-related therapies associated with cardiac dysfunction include the
anthracyclines and trastuzumab (Herceptin), the monoclonal antibody
(Mab) targeted against human epidermal growth factor receptor
(HER2)/neu.1,2 This article will examine the most common cardiotoxic cancer-related drug therapies.
The anthracyclines, which include doxorubicin, daunorubicin,
epirubicin, idarubicin, and valrubicin, are chemotherapeutic antibiotics
that inhibit enzyme topoisomerase II. This inhibition prevents DNA and
RNA from fusing by the intercalation of DNA base pairs and steric
hindrance. Doxorubicin (Adriamycin), one of the major anthracyclines
used in chemotherapy (ChT), is indicated to treat many different
cancers, including breast cancer (BC), acute lymphocytic leukemia (ALL),
lymphoma, acute myeloid leukemia, soft-tissue and bone sarcoma, ovarian
cancer, gastric cancer, bladder cancer, neuroblastoma, Wilms’ tumor,
small cell lung cancer (SCLC), and thyroid cancer.3-9
Anthracyclines are known for their potent cardiotoxic effects,
predominantly heart failure (HF) and cardiomyopathies. Baseline and
periodic measurements of left ventricular ejection fraction (LVEF) are
therefore essential. A multiple gated acquisition (MUGA) scan or
echocardiogram (ECHO) should be performed at baseline for proper
assessment of LVEF. MUGA, a noninvasive procedure used to measure
cardiac function, can locate the part of the heart muscle that has been
damaged and evaluate the type of damage. ECHO uses sound waves to
produce images of the heart to determine how fast the heart is beating
and pumping blood.3-9
Anthracycline-associated cardiotoxicity (AAC) is cumulative and
permanent. The three types of AAC are immediate, early-onset, and
chronic progressive cardiotoxicity. The primary risk factor for AAC is
the cumulative lifetime dose (CLD) of the anthracycline. The CLD must be
documented and retained for proper drug dosage, patient safety, and
positive therapeutic outcomes. Patients are predisposed to the
development of congestive heart failure (CHF) when the CLD is exceeded (TABLE 1).3-9
The main mechanism of action (MOA) for AAC is hypothesized to be the
generation of oxygen free radicals, which cause oxidative stress,
resulting in cellular damage in the cardiomyocyte and eventually
apoptosis, which is directly correlated with the dose of anthracycline
administered. Iron accumulation occurs through both enzymatic and
nonenzymatic channels precipitated by free-radical generation and
redox-associated injury to the cardiomyocyte. As mitochondrial damage
occurs, calcium levels rise, inhibiting the action of the sarcoplasmic
reticulum and decreasing the function of the sodium-potassium pump. All
of these factors are implicated in AAC.3-9
Risk factors for AAC include prior anthracycline therapy, the drug’s
CLD, younger age at treatment initiation, current pregnancy, doxorubicin
dose ≥300 mg/m2, epirubicin ≥600 mg/m2, mediastinal radiation (RT), combination ChT regimens, and increased overall survival.3-8
Carvedilol (Coreg), a nonselective beta-blocker providing adrenergic
blockade, is approved to treat HF, hypertension (HTN), and impaired left
ventricular function following myocardial infarction (MI). Clinical
studies have evaluated its use in the prevention of
anthracycline-induced cardiomyopathy. Subjects received either placebo
or carvedilol 12.5 mg once daily prior to the start of ChT, and the
primary endpoint was systolic function. There was less mortality in the
carvedilol group, but the results were nonsignificant.10
Administration of anthracyclines to adult patients via slow infusion
versus bolus causes lower drug peak levels and reduces the
pharmacokinetic factor of cardiotoxicity. Decreasing the peak drug level
of an anthracycline has a cardioprotective effect. Other measures for
reducing AAC include liposomal anthracycline preparations and
In these agents, liposomes—which have a bilayer phospholipid
covering—are used to encapsulate the anthracycline, mitigating the
potential for cardiac-related drug-induced damage. The liposomal
encapsulation alters the pharmacokinetics and tissue distribution of
doxorubicin, and the liposome increases the half-life of the
anthracycline preparation. The bilayer phospholipid covering reduces the
amount of drug exposed to heart muscle, and the slow release of
anthracycline prevents high peak plasma levels of the drug.12-20
Liposomal agents include liposomal daunorubicin (DaunoXome),
pegylated liposomal doxorubicin (Caelyx, Doxil), and liposomal
doxorubicin (Myocet). These products do not possess the identical amount
of lipid, and the addition of polyethylene glycol to the liposome
alters the pharmacodynamics of the agent. The pegylated product protects
the anthracycline from phagocytosis. Liposomal agents should not be
substituted for the conventional form of the anthracycline.12-20
Liposomal daunorubicin has exhibited cardiotoxicity at cumulative doses of 600 to 900 mg/m2.
Currently, insufficient published data are available to assess the
cardiotoxicity of liposomal daunorubicin versus conventional
Liposomal doxorubicin is associated with a lower rate of cardiotoxic
events compared with conventional doxorubicin. The clinical activity of
liposomal doxorubicin is comparable to that of nonliposomal doxorubicin.
The pegylated liposomal form of doxorubicin has the lowest rate of
cardiotoxicity associated with therapy. At a cumulative dose of >500
mg/m2, pegylated liposomal doxorubicin had a much lower rate
of cardiotoxicity than nonliposomal doxorubicin. Patients with LVEF
<50% should not receive liposomal anthracycline therapy. When the
cumulative dose of the liposomal anthracycline reaches 400 mg/m2, MUGA should be performed and repeated thereafter for cumulative dose increases of 100 to 120 mg/m2.
If clinical cardiotoxicity develops, the liposomal preparation should
be discontinued. If any type of cardiac decompensation is noted, a
diagnostic heart evaluation should be performed.12-20
Dexrazoxane is a cardioprotective agent used in women with metastatic
BC who have received a cumulative dose of doxorubicin of ≥300 mg/m2. It is given at a 10:1 ratio (e.g., dexrazoxane 500 mg/m2:doxorubicin 50 mg/m2)
to prevent cardiomyopathies. Dexrazoxane reduces the severity and
incidence of doxorubicin-associated cardiomyopathies. The agent inhibits
free radical formation, thereby limiting the cardiotoxicity of
doxorubicin, but it may also decrease doxorubicin’s antitumor effects.21
HER2/neu is a transmembrane tyrosine kinase that is overexpressed in
20% to 30% of patients with invasive BC. Trastuzumab is a humanized Mab
directed against HER2/neu-positive (+) cells. It is indicated for
patients with HER2-overexpressing breast, metastatic gastric, and
gastroesophageal junction adenocarcinoma. Trastuzumab binds to the
extracellular domain of the HER2/neu receptor, inhibiting cells that
overexpress HER2/neu. The agent causes antibody-dependent cellular
Early clinical trials of trastuzumab noted cases of CHF and decreases
in LVEF. Cardiotoxicity was noted in 5% of trastuzumab patients on
monotherapy, 13% of patients receiving combination therapy with
paclitaxel, and 27% of patients receiving combination therapy with an
Risk factors for trastuzumab-related cardiotoxicity include
dyslipidemia, diabetes, age ≥50 years, BMI >30, sequential
administration of ChT, diminishing LVEF prior to therapy, and prior
treatment with anthracyclines (cumulative dose >300 mg/m2). Trastuzumab-associated cardiotoxicity, unlike AAC, is reversible.22-24
The greatest risk of trastuzumab-related cardiotoxicity occurs when
the drug is given in combination with an anthracycline.
Non–anthracycline-containing combination regimens with similar
therapeutic efficacy are preferred. Cardiovascular events involving
trastuzumab include reduced heart function, HTN, irregular heartbeat,
CHF, MI, and death. The patient’s heart function should be monitored
prior to initiation and during therapy.22-24
Trastuzumab’s long half-life, which ranges from 2 to 12 days
depending upon the dosage, may contribute to a lack of improvement in a
patient’s cardiac symptoms after discontinuation. Cardiomyocytes are not
destroyed by trastuzumab but appear normal, with changes noted only by
electron microscopy. Trastuzumab causes left ventricular systolic
dysfunction (LVSD) by binding to the extracellular portion of the
HER2/neu receptor. This is known as type II ChT-related cardiac dysfunction
(CRCD), which is usually reversible, with a recovery period of 2 to 4
months. Type II CRCD is not dose-related and does not cause
ultrastructural abnormalities. Anthracyclines induce type I myocardial
damage, which is permanent and cumulative dose–related and may recur,
depending upon additional cardiac stress.22-24
Trastuzumab should be withheld in patients exhibiting a ≥16% decrease
in LVEF from initial levels. If LVEF is less than normal standardized
levels and there is a ≥10% decrease from initial levels, therapy should
be withheld. Therapy may be reinstituted within 4 to 8 weeks if LVEF
returns to normal and there is no decrease from initial levels. Patients
with persistent cardiomyopathies on three occasions or with an LVEF
decrease lasting >8 weeks should discontinue trastuzumab.22-24
Ado-trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug
conjugate consisting of humanized Mab trastuzumab (T) linked to a
maytansine derivative (DM1). It exerts the pharmacologic properties of a
vinca alkaloid via the stable thioether linker MCC
(4-[N-maleimidomethyl] cyclohexane-1-carboxylate). T-DM1 is indicated
for use in HER2+ metastatic BC patients who received prior therapy with a
taxane plus trastuzumab sequentially or in combination. It is dosed at
3.6 mg/kg once every 3 weeks until the disease advances or the patient
experiences intolerable toxicity.25,26
T-DM1 was approved following the international phase III open-label
EMILIA trial, which randomized 991 patients to either T-DM1 (n = 495) or
lapatinib plus capecitabine (L-C) (n = 496). Inclusion criteria
included a baseline LVEF of ≥50% assessed by MUGA or ECHO prior to
enrollment. Patients with serious cardiac arrhythmias, unstable angina,
MI, or symptomatic CHF were excluded. During the trial, most patients
had a consistent LVEF of ≥45% (97.1% of T-DM1 patients vs. 93% of L-C
patients). Three patients in each group had an LVEF ≤40% from baseline
levels. Eight T-DM1 patients (1.7%) and seven L-C patients (1.6%) had an
LVEF of <50% and ≥15% below baseline. At the time trial results were
published, no L-C patients and one T-DM1 patient had developed grade 3
There is no literature concerning the use of T-DM1 in patients with
an LVEF of <50% prior to commencement of therapy. T-DM1 therapy
should be withheld if LVEF is <40% or between 40% and 45% with a ≥10%
decrease below initial levels. LVEF should be retested in 3 weeks; if
there is no improvement, therapy should be permanently discontinued.
Assessment of LVEF prior to initiation of T-DM1 is indicated, and LVEF
should be monitored once every 3 months during therapy.25,26
Alkylating agents bind to N7-guanine, inhibiting DNA replication and
transcription. Cases of endomyocardial and pericardial fibrosis have
been noted with busulfan. These cases, with an onset of 4 to 9 years
post therapy, occurred in patients who received doses >600 mg.5,27
Cyclophosphamide-associated cardiotoxicity is related to the total
dose administered, rather than to cumulative dosing. Patients receiving
bone marrow transplants usually receive high doses of cyclophosphamide
and therefore are predisposed to a higher level of drug-induced
cardiotoxicity. Previous anthracycline therapy and mediastinal RT are
predisposing factors that contribute to cyclophosphamide cardiotoxicity.
Other cardiac events associated with cyclophosphamide therapy include
pericarditis, HF, and myocarditis. The hypothesized MOA is a toxic
metabolite that causes myocytic and endothelial injury. These toxic
effects are usually acute and last for approximately 6 days.5,27
Ifosfamide (Ifex) has been reported to cause dose-related arrhythmias
and HF. Cisplatin, a platinum agent, can also cause HTN, which may be
precipitated by the drug’s dose-limiting effect of nephrotoxicity.
Electrolyte imbalances such as hypokalemia and hypomagnesemia can
predispose cisplatin patients to the development of cardiac arrhythmias.
Other cardiac dysfunctions associated with cisplatin include increased
cardiac enzymes that may indicate MI, palpitations, and chest pain.
Patients receiving combination ChT with cisplatin and cyclophosphamide
have developed HF. Patients treated with cisplatin for metastatic
testicular cancer have developed myocardial ischemia, MI, LV
hypertrophy, and HTN 10 to 20 years post therapy.5,27
Mitomycin is indicated for gastric and pancreatic cancer. When used
in combination with an anthracycline, mitomycin has been associated with
cardiomyopathies. These cardiomyopathies are probably related to the
cumulative dose. Cardiotoxic effects may be produced by superoxide
radicals, which are created when mitomycin is reduced under aerobic
conditions to a semiquinone radical.5,27
Fluorouracil (5-FU) cardiotoxicity, which occurs at a rate of 1% to
68%, usually manifests within 72 hours after administration. Angina is
the most common symptomatic cardiac effect of 5-FU therapy. Arrhythmias,
MI, cardiogenic shock, HF, and sudden death have occurred. Risk factors
associated with 5-FU–related cardiotoxicity include prior mediastinal
RT, past medical history of coronary artery disease (CAD), and
combination therapy with cisplatin. Continuous infusion of 5-FU and
doses >800 mg/m2 predispose patients to a greater rate of cardiotoxicity.5,27
Capecitabine (Xeloda) has a cardiotoxic rate ranging from 3% to 9%.
Patients can develop symptoms of angina within 3 hours to 4 days after
therapy initiation. The main risk factor for cardiotoxic events is a
past medical history of CAD.5,27
Possible MOAs of fluoropyrimidine-induced cardiotoxicity include
autoimmune response, coagulation-system activation, coronary artery
thrombus, protein kinase C–mediated vasospasm, and toxicity to the heart
TYROSINE KINASE INHIBITORS
Tyrosine kinase inhibitors (TKIs), unlike chemotherapy, do not kill
nonmalignant cells, but are targeted to a specific receptor. TKIs are
enzymes that cause the exchange of a phosphate residue from adenosine
triphosphate (ATP) to tyrosine residues in other proteins (substrates).
Because TKIs target only malignant cells, their toxicity profile is less
severe than that of a ChT agent. There are two types of TKIs: Mabs,
which target the external growth factor receptor, and small molecular
entities, which target receptor and nonreceptor TKIs. Cardiotoxicity is
one of the most prominent adverse effects (AEs) of TKI therapy.28
Cardiovascular side effects of TKI therapy include QT prolongation,
acute coronary syndromes, HF, and left ventricular dysfunction. The two
types of toxicity associated with TKI therapy are on-target toxicity and
off-target toxicity. On-target toxicity occurs when the tyrosine
kinase responsible for regulating the production and/or life of the
cancer cell also is deeply involved in the cardiomyocyte’s survival.
When the cardiomyocyte is inhibited, cardiac dysfunction begins.
Inhibition of a kinase that is not the original target of the TKI
results in off-target toxicity. Off-target toxicity is associated
with multitargeting and TKI nonselectivity. This type of nonselectivity
causes an increase in AEs from the TKI.28
Systolic dysfunction causing HF is one of the most prominent AEs of
TKI therapy. Pathways that regulate survival of normal cells, such as
cardiomyocytes, also cause the pathologic survival and abnormal
proliferation of malignant cells. Geriatric patients, renal patients,
and patients with prior cardiovascular-associated dysfunction are
predisposed to cardiac dysfunction from TKIs.28
Profiles of Individual TKIs
Imatinib: Imatinib (Gleevec) is used for all
phases of Philadelphia chromosome+ (PH+) chronic myelogenous leukemia
(CML) and also for gastrointestinal stromal tumors (GISTs). Imatinib
inhibits Bcr-Abl tyrosine kinase and is associated with cardiac
disorders such as pulmonary edema, tachycardia, palpitations, CHF,
pericardial effusion, angina pectoris, MI, cardiac arrest, atrial
fibrillation, and arrhythmias.29
Dasatinib: Dasatinib (Sprycel) is a TKI for
newly diagnosed chronic-phase CML patients or CML patients intolerant or
resistant to imatinib therapy, as well as for PH+ ALL patients
resistant or intolerant to previous treatment. Patients on dasatinib
therapy must be monitored for cardiac dysfunction such as QT
Nilotinib: Nilotinib (Tasigna) is indicated for CML.
Patients have experienced QT prolongation and precipitous fatal events.
These fatal events have occurred in Ph+ CML patients resistant or
intolerant to therapy and are associated with ventricular
repolarization. ECG should be done at baseline and 7 days after therapy
initiation. ECGs should be performed regularly thereafter and after any
Prior to therapy initiation, electrolyte disturbances such as
hypokalemia and hypomagnesemia must be corrected. Patients with these
electrolyte disturbances or long QT syndrome should not receive
nilotinib. The use of strong CYP3A4 inhibitors and other drugs that may
lengthen the QT interval should be avoided. Patients who must receive a
strong CYP3A4 inhibitor should be considered for a dosage reduction and
be closely monitored by a healthcare professional. Sudden death has been
reported in patients with resistant or intolerant Ph+ CML who received
nilotinib; ventricular-repolarization abnormalities may have contributed
to this occurrence.31
Ponatinib: Ponatinib (Iclusig) is indicated for
patients with CML (all phases) intolerant or resistant to previous
treatment or for Ph+ ALL patients with the T315I+ mutation who are
resistant to TKI therapy with a starting dose of 45 mg orally per day.
Fatal MI, arterial thrombosis, and stroke have occurred. Arrhythmias,
CHF (4%), CAD, angina, stroke, transient ischemic attack (TIA )(2%), HTN
(67% treatment-emergent), and hypertensive crisis (<1%) are AEs of
ponatinib therapy. Patients should be monitored for symptoms of
arrhythmias and for signs and symptoms of CHF while on ponatinib. In a
clinical study, 11% of ponatinib patients experienced arterial events
and 8% of patients experienced serious arterial events. If serious
arterial thrombosis develops, ponatinib should be discontinued.32
A small ponatinib study assessed patients for the development of QTc
prolongation. No changes >20 ms from baseline were noted; however,
owing to the small sample size, the possible development of QTc
prolongation with this agent cannot be excluded. Ponatinib has a Risk
Evaluation and Mitigation Strategy program that includes a new boxed
warning, safety information, and dosing recommendations for prescribers.
The boxed warning provides information on vascular occlusive episodes
and a new warning regarding HF.32
Lapatinib: Lapatinib is used in combination with
capecitabine for HER2/neu+ BC. Patients’ LVEF should be evaluated at
baseline and during therapy. In a clinical trial, most decreases in LVEF
(>57%) occurred during the first 12 weeks of therapy. Lapatinib
should be discontinued in patients experiencing an LVEF decrease of
grade 2 or greater or those with an LVEF lower than standardized.
Electrolyte disturbances such as hypokalemia and/or hypomagnesemia can
precipitate QT-interval prolongation. ECG monitoring may be essential in
this subset of patients.33
Sunitinib: Sunitinib (Sutent) is a multitargeted TKI
indicated for various malignancies, including renal cell cancer (RCC),
GISTs, and pancreatic neuroendocrine tumors. Sunitinib has been
associated with bradycardia and QTc-interval prolongation. The dose
administered directly correlates with the drug’s effect on the QT
interval. Sunitinib also induces CHF, with an incidence of up to 33.8%
in RCC patients. ATP depletion resulting from ribosomal depletion and
activation of an intrinsic apoptotic pathway is the MOA for
sunitinib-induced cardiotoxicity, which is considered to be an
off-target effect. Sunitinib patients have a greater rate of HF owing to
the inhibition of vascular endothelial growth factor (VEGF) signaling.34
Bortezomib, which is indicated for multiple myeloma and mantle cell
lymphoma, has resulted in the development and worsening of HF. Patients
with underlying cardiac dysfunction or risk factors should be closely
monitored while on therapy.35
Bortezomib therapy has resulted in incidences and exacerbations of
CHF. The proposed MOA for this cardiac dysfunction is possible
dysregulation of the ubiquitin-proteasome system. When bortezomib
inhibits the proteasome system, polyubiquitinated proteins accumulate,
causing cardiac dysfunction by enabling systemic inhibition of the
Paclitaxel (Taxol) and docetaxel (Taxotere) work by promoting
microtubule assembly and inhibiting microtubule disassembly. Bradycardia
is the main cardiotoxic AE, with an incidence of 0.5% to 5% in
paclitaxel patients and an incidence of 1.7% in docetaxel patients.
Paclitaxel, which has proarrythmogenic properties, is associated with
atrioventricular block, hypotension, sinus bradycardia, ventricular
tachycardia, ischemia, and CHF. Paclitaxel affects the Purkinje system
either directly with its chronotropic effects or indirectly through its
Cremophor EL vehicle, which triggers the release of histamine and
Vinca alkaloids are antimicrotubule agents used primarily for
lymphoma and leukemia patients. ECG changes, angina, MI, and myocardial
ischemia have been noted with vinca alkaloids. Women experience more
cardiotoxic effects from vinorelbine than do men. Vinca
alkaloid–associated cardiotoxicity may be mediated by coronary spasm,
which causes ischemia.36
Agents such as bevacizumab, sunitinib, sorafenib, pazopanib,
ziv-alflibercept, and vandetanib have caused an approximately 50%
increase in HTN in patients previously or currently receiving therapy.37-39
Bevacizumab (Avastin) is also an Mab and a VEGF inhibitor indicated
for use in metastatic colorectal cancer, nonsquamous non-SCLC,
glioblastoma, and metastatic RCC. There is an approximate 5% incidence
of HTN in bevacizumab patients. VEGF inhibition enables nitric oxide
suppression and prostacyclin activity in the endothelium is decreased,
thereby causing the elevation in blood pressure (BP). Bevacizumab is
noted for venous and arterial thromboembolic events (ATEs) including MI
and cerebral infarction. Serious AEs and ATEs, including TIAs, angina,
MI, and cerebral infarction, have occurred. Combination ChT with
bevacizumab conferred an increased risk of ATE in patients aged ≥65
years. Patients who experience a severe ATE should not resume
Patients with uncontrolled BP are not candidates for bevacizumab
therapy. BP should be monitored every 2 to 3 weeks during therapy.
Antihypertensive agents commonly used to treat bevacizumab-induced HTN
include calcium channel blockers and ACE inhibitors. Bevacizumab
patients may also develop asymptomatic proteinuria. Patients with
proteinuria exceeding 2 g within 24 hours should not receive bevacizumab
therapy. Key factors in managing bevacizumab-induced HTN include
patient education, home BP monitoring, and adjustment of medication as
Arsenic trioxide (Trisenox) is indicated for patients with relapsed
or refractory acute promyelocytic leukemia (APL). A 12-lead ECG should
be performed before arsenic therapy initiation. Patients may experience
QT prolongation and should receive appropriate electrolyte monitoring,
with potassium levels maintained at >4 meq/L and magnesium levels
maintained at >1.8 mg/dL during therapy. Other cardiac AEs include
torsades de pointes, sinus tachycardia, and fluid retention with
pericardial and pleural effusions. Patients should be monitored
following infusion therapy.36
All-trans retinoic acid (ATRA; Tretinoin), which is indicated for APL, is given orally at 45 mg/m2
per day in combination with an anthracycline plus or minus cytarabine
in two equally divided doses until complete remission or for 90 days.
Retinoic acid syndrome (RAS) can develop in approximately 26% of ATRA
patients within the first 21 days of therapy. Pericardial and pleural
effusions, hypotension, fever, and dyspnea are hallmarks of RAS.
Approximately 17% of patients studied experienced decreased LVEF.
Thrombosis and fatal MI have been noted in ATRA patients.36
Cardiotoxic cancer-related therapies present a management challenge
for healthcare professionals. This morbid condition can be appropriately
managed by properly educating health professionals and ensuring proper
therapy administration. Cardiac-related imaging, biomarkers, and
genetics are possible future sources of research strategies designed to
mitigate the cardiotoxicity associated with cancer-related therapies.
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