scholarly journals Early cardiotoxicity after adjuvant concomitant treatment with radiotherapy and trastuzumab in patients with breast cancer

2018 ◽  
Vol 52 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Tanja Marinko ◽  
Simona Borstnar ◽  
Rok Blagus ◽  
Jure Dolenc ◽  
Cvetka Bilban-Jakopin
Keyword(s):  
Breast Cancer ◽  
Pericardial Effusion ◽  
Left Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Concomitant Treatment ◽  
Ventricular Ejection Fraction ◽  
Cancer Group ◽  
Breast Cancer Group ◽  
The Right

Abstract Background The purpose of the study was to find out whether there is a difference in the early parameters of cardiotoxicity (left ventricular ejection fraction [LVEF] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) between the two groups of patients: the patients treated for left breast cancer (left breast cancer group) and those treated for the right breast cancer (right breast cancer group), after the treatment had been completed. Patients and methods The study included 175 consecutive patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer, treated concurrently with trastuzumab and radiotherapy (RT), between June 2005 and December 2010. Echocardiography with LVEF measurement was performed before adjuvant RT (LVEF0) and after the completed treatment (LVEF1,). After the treatment NT-proBNP measurement was done as well. The difference (Δ) between LVEF0 and LVEF1 was analysed (Δ LVEF = LVEF0 - LVEF1) and compared between the two groups. Results There were 84 patients in the left and 91 in the right breast cancer group. Median observation time was 57 (37–71) months. Mean Δ LVEF (%) was -1.786% in the left and -2.607% in the right breast cancer group (p = 0.562, CI: -2.004 to 3.648). Median NT-proBNP were 111.0 ng/l in the left and 90.0 ng/l in the right breast cancer group (p = 0.545). Echocardiography showed that the patients in the left breast cancer group did not have significantly worse systolic and diastolic left ventricular function in comparison with the patients in the right breast cancer group, but, they had higher incidence of pericardial effusion (9 [11%] vs. 1 [1%]) (p = 0.007). Conclusions We did not find any significant differences in the early parameters of cardiotoxicity (LVEF, NT-proBNP) between the observed groups. Patients who received left breast/chest wall irradiation had higher incidence of pericardial effusion.

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.

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.

Abstract 17055: Novel Dual mTOR Inhibitor/AMPK Activator Mitigates Doxorubicin Cardiotoxicity and Potentiates Its Chemotherapeutic Efficacy Against Triple Negative Breast Cancer

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anindita Das ◽  
Sahak Hovsepian ◽  
Sayantanee Das ◽  
Arun Samidurai ◽  
Adolfo G Mauro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Mtor Inhibitor ◽  
Triple Negative ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Chemotherapeutic Efficacy

Background: Doxorubicin (DOX) is a first-line anticancer drug for the treatment of triple negative breast cancer (TNBC). However, its dose-dependent delayed and progressive cardiotoxicity limits its therapeutic application. NovoMedix (NM922) is a novel dual mTOR inhibitor/AMPK activator that was shown to attenuate adverse cardiac remodeling and fibrosis in a pressure-overload mouse model of heart failure. We investigated whether combination therapy with DOX and NM922 exhibits synergistic chemotherapeutic effect while mitigating DOX cardiotoxicity. Methods & Results: Tumors were generated in athymic female BALB/cAnNCr-nu/nu mice by implanting MDA-MB-231 cells into the rear right flank. Mice with tumors (volume≈200mm 3 ) were randomized into 6 groups and treated as follows: 1) Control (n=10); 2) DOX (3 mg/kg; i.p. twice weekly, total 15 mg/kg; n=10); 3) NM922 (25 mg/kg/d; p.o. n=5); 4) DOX+NM922 (25 mg/kg/d; p.o. n=15); 5) NM922 (100 mg/kg/d; p.o. n=5); 6) DOX+NM922 (100 mg/kg/d; p.o. n=15). Tumor size, body weight and cardiac function were assessed throughout the study. DOX alone, and to a significant extent when in combination with NM922 (25 mg/kg) reduced tumor growth compared to control. NM922 (100 mg/kg) with/without DOX significantly reduced tumor growth as compared to DOX alone (Fig A). DOX caused reduction in body weight and survival of tumor-bearing mice. NM922 did not prevent DOX-induced cachexia, but significantly improved survival in DOX-treated mice (Fig B). DOX treatment caused a significant decline in left ventricular ejection fraction compared to control over 3 weeks, which was ameliorated with NM922 (100 mg/kg) co-treatment (Fig C&D). Conclusion: Our results suggest that NM922 may potentiate the chemotherapeutic efficacy of DOX in TNBC, while mitigating its cardiotoxicity. Moreover, these findings advocate the potential efficacy of utilizing lower DOX dosages when combined with NM922, which would have significant clinical implications.

scholarly journals Incidence of Cardiotoxicity and Validation of the Heart Failure Association- International Cardio-Oncology Society risk stratification Tool in Patients Treated with Trastuzumab for HER2-Positive Early Breast Cancer.

2021 ◽  
Author(s):  
Nicolò Matteo Luca Battisti ◽  
Maria Sol Andres ◽  
Karla A Lee ◽  
Tharshini Ramalingam ◽  
Tamsin Nash ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Early Breast Cancer ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Very High

Abstract PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity

scholarly journals Effects of Exercise on Cardiac Function Outcomes in Women Receiving Anthracycline or Trastuzumab Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (18) ◽  
pp. 8336
Author(s):  
Pedro Antunes ◽  
Dulce Esteves ◽  
Célia Nunes ◽  
Anabela Amarelo ◽  
José Fonseca-Moutinho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cardiac Function ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cochrane Library ◽  
Circulating Biomarkers ◽  
Ventricular Ejection Fraction ◽  
Secondary Outcomes

Background: we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of exercise training on cardiac function and circulating biomarkers outcomes among women with breast cancer (BC) receiving anthracycline or trastuzumab-containing therapy. Methods: PubMed, EMBASE, Cochrane Library, Web of Science and Scopus were searched. The primary outcome was change on left ventricular ejection fraction (LVEF). Secondary outcomes included diastolic function, strain imaging and circulating biomarkers. Results: Four RCTs were included, of those three were conducted during anthracycline and one during trastuzumab, involving 161 patients. All trials provided absolute change in LVEF (%) after a short to medium-term of treatment exposure (≤6 months). Pooled data revealed no differences in LVEF in the exercise group versus control [mean difference (MD): 2.07%; 95% CI: −0.17 to 4.34]. Similar results were observed by pooling data from the three RCTs conducted during anthracycline. Data from trials that implemented interventions with ≥36 exercise sessions (n = 3) showed a significant effect in preventing LVEF decline favoring the exercise (MD: 3.25%; 95% CI: 1.20 to 5.31). No significant changes were observed on secondary outcomes. Conclusions: exercise appears to have a beneficial effect in mitigating LVEF decline and this effect was significant for interventions with ≥36 exercise sessions.

scholarly journals Cardiac Energetics Before, During and After Anthracycline-based Chemotherapy in Breast Cancer Patients Using 31P Magnetic Resonance Spectroscopy: A Pilot Study

2020 ◽  
Author(s):  
Gillian Macnaught ◽  
Olga Oikonomidou ◽  
Christopher T. Rodgers ◽  
William Clarke ◽  
Annette Cooper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Resonance Spectroscopy ◽  
Ventricular Ejection Fraction ◽  
Time Points ◽  
Change In Mean

Abstract PURPOSETo explore the utility of phosphorus magnetic resonance spectroscopy (31P MRS) in identifying anthracycline-induced cardiac toxicity in patients with breast cancer.METHODS20 patients with newly diagnosed breast cancer receiving anthracycline-based chemotherapy had cardiac magnetic resonance assessment of left ventricular ejection fraction (LVEF) and 31P MRS to determine myocardial Phosphocreatine/Adenosine Triphosphate ratio (PCr/ATP) at three time points: pre, mid and end-chemotherapy. Plasma high sensitivity cardiac troponin-I (cTn-I) tests and electrocardiograms were also performed at these same time points. RESULTS PCr/ATP ratio did not change significantly between pre- and mid-chemo (2.16±0.46 v 2.00±0.56, p=0.80) and pre- and end-chemo (2.16±0.46 v 2.17±0.86, p=0.99). Mean LVEF reduced significantly by 5.1% between pre- and end-chemo (61.4±4.4 vs 56.3±8.1 %, p=0.02). Change in PCr/ATP ratios from pre- to end-chemo correlated inversely with changes in LVEF over the same period (r=-0.65, p=0.006). Plasma cTn-I increased progressively during chemotherapy from pre- to mid-chemo (1.35±0.81 to 4.40±2.64 ng/L; p=0.01) and from mid to end-chemo (4.40±2.64 to 18.33±13.23 ng/L; p=0.001). CONCLUSIONSIn this small cohort pilot study, we did not observe a clear change in mean PCr/ATP values during chemotherapy despite evidence of increased plasma cardiac biomarkers and reduced LVEF. Future similar studies should be adequately powered to take account of patient drop-out and variable changes in PCr/ATP.

Role of the Renin-Angiotensin-Aldosterone System and the Glutathione S-Transferase Mu, Pi and Theta Gene Polymorphisms in Cardiotoxicity after Anthracycline Chemotherapy for Breast Carcinoma

2013 ◽  
Vol 28 (4) ◽  
pp. 336-347 ◽  
Author(s):  
Daniela Vivenza ◽  
Mauro Feola ◽  
Ornella Garrone ◽  
Martino Monteverde ◽  
Marco Merlano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Polymorphisms ◽  
Left Ventricular ◽  
Detoxification Enzymes ◽  
Left Ventricular Ejection ◽  
Glutathione S Transferase ◽  
Renin Angiotensin Aldosterone System ◽  
Ventricular Ejection Fraction ◽  
Renin Angiotensin ◽  
Anthracycline Chemotherapy

Background Anthracyclines are among the most active drugs against breast cancer, but can exert cardiotoxic effects eventually resulting in congestive heart failure (CHF). Identifying breast cancer patients at high risk of developing cardiotoxicity after anthracycline therapy would be of value in guiding the use of these agents. Aims We determined whether polymorphisms in the renin-angiotensin-aldosterone system (RAAS) and in the glutathione S-transferase (GST) family of phase II detoxification enzymes might be useful predictors of left ventricular ejection fraction (LVEF) kinetics and risk of developing CHF. We sought correlations between the development of cardiotoxicity and gene polymorphisms in 48 patients with early breast cancer treated with adjuvant anthracycline chemotherapy. Methods We analyzed the following polymorphisms: p.Met235Thr and p.Thr174Met in angiotensinogen ( AGT), Ins/Del in angiotensin-converting enzyme ( ACE), A1166C in angiotensin II type-1 receptor ( AGTR1A), c.-344T>C in aldosterone synthase ( CYP11B2), p.Ile105Val in GSTP1. Additionally, we analyzed the presence or absence of the GSTT1 and GSTP1 genes. A LVEF <50% was detected at least once during the 3 years of follow-up period in 13 out of 48 patients (27.1%). Conclusion RAAS gene polymorphisms were not significantly associated with the development of cardiotoxicity. GSTM1 may be useful as a biomarker of higher risk of cardiotoxicity, as demonstrated in our cohort of patients (p=0.147).

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