scholarly journals Cardiovascular toxicity of antitumor therapy: effect on myocardial and vascular remodeling

2021 ◽  
Vol 20 (7) ◽  
pp. 2923
Author(s):  
Yu. Yu. Kirichenko ◽  
I. S. Ilgisonis ◽  
T. V. Ivanova ◽  
A. S. Zolotukhina ◽  
N. V. Khabarova ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Healthy Volunteers ◽  
Cancer Patients ◽  
Normal Values ◽  
Vascular Wall ◽  
Stiffness Index ◽  
Left Ventricular Ejection ◽  
Cardiovascular Toxicity ◽  
Cardiac Hemodynamics ◽  
Multiagent Chemotherapy

Aim. To study the effect of multiagent chemotherapy on structural and functional vascular, electrophysiological parameters and cardiac hemodynamics in patients with stomach cancer.Material and methods. The study included 3 groups of 25 people: healthy volunteers, those with established cardiac disease (hypertension + coronary artery disease), gastric adenocarcinoma (fluoropyrimidine/platinum-based chemotherapy). Cancer patients before and after chemotherapy courses underwent non-invasive assessment of vascular wall and endothelial dysfunction (videocapillaroscopy, digital photoplethysmography), as well as electrocardiography and echocardiography. Healthy volunteers and cardiac patients were examined once.Results. In cancer patients, even before chemotherapy courses, endothelial dysfunction (ED) (occlusal index, 1,7 (1,4; 1,9), normal values >1,8) and structural vascular disorders (stiffness index, 8,9 m/s (7,7; 9,7), normal values <8 m/s; refractive index, 32,4% (27,5; 37,7), normal values <30%). All above-mentioned parameters significantly worsened after multiagent chemotherapy (progression of ED and vascular wall remodeling: occlusal index, 1,3 (1,2; 1,5) (p<0,0002); stiffness index, 10,3 m/s (9,5; 11,2) (p<0,0001); reflection index, 40,2% (35,5; 43,6) (p<0,001) Decrease in left ventricular ejection fraction and diastolic function was detected. The number of supraventricular and ventricular premature beats during chemotherapy increased 9 and 10 times, respectively (p<0,05).Conclusion. The study for the first time assessed the effect of multiagent chemotherapy on ED, vascular stiffness and cardiac hemodynamics in patients with gastric cancer. A significant aggravation of all endothelial function parameters after treatment has been proven, which requires further study in order to develop criteria for early cardiovascular toxicity. 

scholarly journals The effect of chemotherapy on endothelial function and microcirculation in patients with gastric cancer

Kardiologiia ◽  
2020 ◽  
Vol 60 (2) ◽  
pp. 89-95
Author(s):  
Yu. Yu. Kirichenko ◽  
I. S. Ilgisonis ◽  
Yu. N. Belenkov ◽  
E. V. Privalova ◽  
Yu. I. Naymann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endothelial Dysfunction ◽  
Healthy Volunteers ◽  
Cancer Patients ◽  
Vascular Diseases ◽  
Vascular Wall ◽  
Capillary Network ◽  
Wall Stiffness ◽  
Before And After ◽  
Cardio Vascular

Objective. To evaluate and study the dynamics of endothelial dysfunction instrumental indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer (adenocarcinoma) before and after chemotherapy; compare it with the results obtained from healthy volunteers and patients with cardio-vascular diseases.Materials and Methods. The study included 65 people: 25 healthy volunteers, 15 patients with known cardio-vascular diseases (CVD) and 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage 2—4 who underwent surgical treatment followed by chemotherapy according to the FOLFOX, XELOX, and XP regimes. For non-invasive assessment of the vascular wall’s state of large vessels and microcirculation, all patients in the main group underwent computer nailfold capillaroscopy and finger photoplethysmography before chemotherapy and within a month after the completion of the last course. For healthy volunteers and patients with CVD, the above studies were performed once during the examination.Results. The data obtained indicate a significant increase in the reflection index of small muscle arteries (RI) and the stiffness index of large conducting arteries (aSI) during chemotherapy. In cancer patients, even before the treatment, endothelial dysfunction was detected, which significantly worsened after treatment (occlusion index (IO) before and after chemotherapy 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p<0.0002, respectively). Significant differences in the compared indices in cancer patients and CVD group were revealed only after chemotherapy. Significant structural and functional disorders of capillaries were noted in the studied groups, which also worsened during chemotherapy in the main group (density of the capillary network at rest 43.23cap/mm2 vs. 42.19cap/mm2, p <0.01, respectively; density of the capillary network after the reactive hyperemia test 46.77cap/mm2 vs. 44.11cap/mm2, p<0,02, respectively).Conclusion. In this study, for the first time, the dynamics of endothelial dysfunction indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer were studied, and a reliable increasing of these changes was proved during chemotherapy. The results indicate the need for a further search for accurate and effective methods of identifying early signs of close and distant vasculotoxicity, the development of individual prevention programs in order to significantly reduce the risk of cardiovascular events during and after chemotherapy.

scholarly journals The Vascular Wall State and Microcirculation Parameters in Patients with Controlled and Uncontrolled Arterial Hypertension

2019 ◽  
Vol 15 (4) ◽  
pp. 495-501
Author(s):  
V. I. Podzolkov ◽  
A. E. Bragina ◽  
D. U. Natkina ◽  
T. A. Safronova ◽  
N. N. Nebieridze ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Arterial Hypertension ◽  
Biochemical Parameters ◽  
Asymmetric Dimethylarginine ◽  
Pulse Wave ◽  
Normal Values ◽  
Vascular Wall ◽  
Cognitive Status ◽  
Significant Relation ◽  
Large Vessels

Aim. To study the rigidity of the vascular wall and microcirculation parameters in patients with uncontrolled (UCAH) and controlled arterial hypertension (CAH).Material and methods. 134 patients with essential hypertension were included, among them 88 (65.7%) patients with UCAH and 46 (34.3%) patients with CAH. Patients in both groups were similar by sex, age, duration of hypertension and some biochemical parameters. Patients had a study of the parameters of stiffness of the vascular wall, microcirculation parameters, as well as an evaluate of the plasma level of asymmetric dimethylarginine (ADMA).Results. Pulse wave velocity (PWV) did not differed between the UCAH and CAH, both in absolute values (1144 [1000-1290] vs 1138 [10281279] cm/sec; p=0.385) and in the frequency of exceeding the normal values (95% vs 92%; p=0.784). Microcirculation index (MI) in CAH was significantly higher than in the UCAH group: 30.55 [27.08-34.4] and 22.82 [18.62-26.05], respectively (p <0.05). ADMA plasma concentration was significantly higher 0.69 [0.62-0.81] μmol/l in UCAH, than in the CAH group 0.62 [0.58-0.70] µmol/l (p <0.05), that shows the presence of endothelial dysfunction. There were detected significant relation between MI and cognitive status.Conclusion. The results of our study indicate the presence of signs of endothelial dysfunction in patients with UCAH with changes in the stiffness of the vascular wall comparable with the CAH group. This may reflect the slower effect of antihypertensive therapy on the remodeling processes of large vessels in comparison with the microvasculature.

scholarly journals Endothelial dysfunction in cancer patients before and after chemotherapy: focus on biomarkers

2021 ◽  
Vol 20 (Supplement_1) ◽  
Author(s):  
A Emelianov ◽  
YU Kirichenko ◽  
I Ilgisonis ◽  
YU Belenkov ◽  
E Privalova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endothelial Dysfunction ◽  
Cancer Patients ◽  
Basic Research ◽  
Vascular Wall ◽  
Platinum Compound ◽  
Normal Ranges ◽  
Endothelin System ◽  
Wall Stiffness ◽  
Before And After

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The reported study was funded by Russian Foundation for Basic Research (RFBR) project number 19-315-90034 Background. Nowadays gastric cancer is one of the leading causes of world cancer mortality. Modern chemotherapy (CT) significantly improves survival and quality of life among these patients. Unfortunately, anticancer drugs induce some biomolecular disorders, which influence endothelial dysfunction and microcirculation lesions, subsequently leading to vasculo- and cardiotoxicity. The aim To study the dynamics of endothelial dysfunction’s (ED) biomarkers (endothelin-1 (ET-1), von Willebrand factor (VWF)) in patients with gastric cancer before and after CT. Material and methods The study included 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage II - IV, who have been treated by CT including platinum compound (oxaliplatin, cisplatin) and fluoropyrimidine group (5-fluorouracil, capecitabine) and are proven to be cardiovasculotoxic. All patients underwent blood tests, computer nailfold capillaroscopy and finger photoplethysmography (non-invasive assessment of vascular wall stiffness and endothelial function), electrocardiography (ECG), 24-hour ECG, echocardiography before CT and within a month after the last course. Results The median patients’ age was 64 ± 13 years; 68% were male; 52% had a prior cardiac illness: arterial hypertension (n = 12, 48%), coronary artery disease (n = 7, 28%), chronic heart failure (n = 3, 12%). The data obtained showed that ET-1 median levels were below normal values and did not change during CT: 0,95pg/ml (0,6;1,4) vs. 0,94pg/ml (0,7;1,4), р&lt;0,9 (N = 1–3pg/ml), before and after CT respectively. The level of VWF remained within normal ranges and did not significantly differ in cancer patients before and after treatment 0,75IU/ml (0,7;0,9) vs. 0,8IU/ml (0,74;0,9), р&lt;0,6 (N = 0,5–1,5IU/ml). Even before CT, endothelial dysfunction was detected, which significantly worsened after the treatment (occlusion index (IO) before and after CT 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p &lt; 0.0002, respectively). During data analysis, significant correlations were found: between ET-1 level and IO (r = 0.554, p = 0,006), ET-1 and percentage of capillary recovery (r= -0.7, p = 0,029) [both parameters characterize functional abnormalities of the microvasculature], ET-1 and the quantity of supraventricular extrasystoles (r=-0.48, p = 0,032). Conclusion In this study, the dynamics of ED biomarkers in patients with gastric cancer were studied. Even though reliable changes were not proven for the assessed molecular parameters ET-1 and VWF during CT (supposing depletion of endothelin system, small patient cohort), the above parameters may be used for identifying early signs of close and long-term cardio/vasculotoxicity due to significant positive correlations with microvasculature lesions. Further bigger trials for identification of other accurate and effective laboratory methods of detecting early features of vasculotoxicity are required.

scholarly journals Stimulated Suicidal Erythrocyte Death in Arteritis

2016 ◽  
Vol 39 (3) ◽  
pp. 1068-1077 ◽  
Author(s):  
Rosi Bissinger ◽  
Daniela S. Kempe-Teufel ◽  
Sabina Honisch ◽  
Syed M. Qadri ◽  
Elko Randrianarisoa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Healthy Volunteers ◽  
Annexin V ◽  
Vascular Occlusion ◽  
Vascular Wall ◽  
Cellular Mechanisms ◽  
Forward Scatter ◽  
Erythrocyte Surface ◽  
Theory Result ◽  
And Oxidative Stress

Background/Aims: Arteritis is an inflammatory disease of the vascular wall leading to ischemia and vascular occlusion. Complications of arteritis include anemia, which could, at least in theory, result from suicidal erythrocyte death or eryptosis, which is characterized by erythrocyte shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include increased cytosolic Ca2+-concentration ([Ca2+]i), oxidative stress and ceramide formation. The present study explored whether and how arteritis influences eryptosis. Methods: Blood was drawn from patients suffering from arteritis (n=17) and from healthy volunteers (n=21). PS exposure was estimated from annexin V-binding, erythrocyte volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) from DCFDA fluorescence and ceramide abundance from FITC-conjugated antibody binding in flow cytometry. The patients suffered from anemia despite 2.8±0.4% reticulocytes. Results: The percentage of PS-exposing erythrocytes was significantly higher in patients (1.1±0.1%) than in healthy volunteers (0.3±0.1%). The increase in PS exposure was paralleled by increase in oxidative stress and [Ca2+]i but not by significant changes of ceramide abundance. Erythrocyte PS exposure and ROS production were significantly enhanced in erythrocytes exposed to patient plasma as compared to exposure to plasma from healthy volunteers. Conclusion: Arteritis is associated with enhanced eryptosis due to increased [Ca2+]i and oxidative stress. The eryptosis contributes to or even accounts for the anemia in those patients. As eryptotic erythrocytes adhere to endothelial cells of the vascular wall, they could impede microcirculation and thus contribute to vascular occlusion.

scholarly journals Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 782
Author(s):  
Sona Ciernikova ◽  
Michal Mego ◽  
Michal Chovanec
Keyword(s):  
Cardiovascular Diseases ◽  
Cancer Survivors ◽  
Cancer Patients ◽  
Gut Microbiome ◽  
Late Effects ◽  
Fecal Microbiota Transplantation ◽  
Experimental Models ◽  
Neurocognitive Disorders ◽  
Cardiovascular Toxicity

Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota–gut–brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

scholarly journals Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Mary Obasi ◽  
Arielle Abovich ◽  
Jacqueline B. Vo ◽  
Yawen Gao ◽  
Stefania I. Papatheodorou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Weighted Mean ◽  
Ventricular Ejection Fraction

Abstract Purpose Cardiotoxicity affects 5–16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. Methods A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s Q test and the I2 test. Results Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27–0.78), p = 0.004, $${ }I^{2}$$ I 2  = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17–1.45), p = 0.20, $$I^{2}$$ I 2  = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75–9.52), p < 0.001, $$I^{2}$$ I 2  = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82–11.68, p = 0.024, $$I^{2}$$ I 2  = 80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusion This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. Trial Registration Number and Date of Registration PROSPERO: CRD42020140352 on 7/6/2020.

Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Effects ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Neo Adjuvant Chemotherapy

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

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