Trastuzumab-related Cardiotoxicity Research Articles

Examining the risk factors for trastuzumab-related cardiotoxicity in a predominantly Hispanic South Texas population: A descriptive study.

e24000 Background: Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), stands as first line treatment for HER2 positive breast cancer. Despite its efficacy, trastuzumab’s association with cardiotoxicity requires monitoring via serial transthoracic echocardiograms (TTEs). We aimed to evaluate the risk factors for trastuzumab related cardiotoxicity in a South Texas population that is uniquely a majority-minority Hispanic population. Methods: A retrospective chart review study was conducted of all female patients with HER2-positive breast cancer who received trastuzumab treatment from 2015-2021. A total of 180 patients were identified. Patients without baseline TTE or a baseline left ventricle ejection fraction (LVEF) less than 53% were excluded. The final sample size included 132 patients. Cardiotoxicity was defined as a decrease in LVEF of more than 10% during the 1-year study period. Results: The mean age at the time of diagnosis in the study population was 54.2 years. The average BMI of the study participants was 30.89. The incidence of cardiotoxicity in this study population was 6%. Among those who developed cardiotoxicity, 50% had hypertension, 25% had hyperlipidemia, 12.5% had type 2 diabetes mellitus, and 12.5% had previous coronary artery bypass surgery (CABG). In terms of cancer treatment, 12.5% of patients had a history of radiation, 25% had a history of anthracycline therapy, and 12.5% had their trastuzumab treatment ended prematurely. Of the cardiotoxicity population, 37.5% patients were former smokers and 25% were former alcohol users. Hispanic/Latino patients composed 58% of the study population and represented 50% of patients who experienced cardiotoxicity. Conclusions: The incidence of trastuzumab-related cardiotoxicity in this Hispanic/Latino majority-minority population was 6%, lower than the 9% observed in a predominantly white population in our previous study. However, further studies are needed to determine the factors contributing to this reduced cardiotoxicity rate in this population.

Trastuzumab-Related Cardiotoxicity in Adjuvant Setting: A Real-World Scenario.

Rachana Chennamaneni Trastuzumab, a humanized monoclonal antibody, significantly improves outcomes in HER 2-neu positive breast cancer. The incidence of cardiotoxicity with trastuzumab is approximately 8 to 10%. This study was designed to analyze the incidence and risk factors associated with trastuzumab-related cardiotoxicity in real-world settings. This was a single institutional retrospective analysis of the incidence of trastuzumab-related cardiotoxicity in nonmetastatic HER 2-positive, invasive breast cancer from January 2013 to December 2018. Trastuzumab-related cardiotoxicity was defined as symptomatic heart failure or asymptomatic decline in left ventricular ejection fraction (LVEF) by more than or equal to 10% or LVEF less than 50%. Risk factors analyzed were higher body mass index (≥30 kg/m 2 ), history of diabetes, hypertension, cardiac disease, left-sided radiotherapy (RT), and prior exposure to anthracyclines. Out of the 246 patients diagnosed with early stage HER 2-positive breast cancer, 117 (47.5%) received trastuzumab and constituted the study population. Trastuzumab-related cardiotoxicity was seen in a total of 16 (13.6%) patients. Eleven (9.4%) patients had an asymptomatic decline, while symptomatic LV dysfunction was seen in five (4.2%) patients. The median baseline ejection fraction was 65% (range, 56-72). The median time to development of cardiotoxicity was 18.5 weeks (range, 3-52) and the median trastuzumab cycle for cardiotoxicity was 6 (range, 2-16). Ten (62.5%) patients were rechallenged with trastuzumab following which one patient developed an asymptomatic decline in ejection fraction and one patient developed symptomatic heart failure. Cardiac-related mortality was seen in one (0.85%) patient. Left-sided RT to chest ( p = 0.012) and presence of more than or equal to two risk factors ( p = 0.01) had significant impact on incidence of cardiotoxicity. Approximately 14% developed trastuzumab-related cardiotoxicity that was slightly higher compared with that seen in clinical trials. Left-sided RT to chest and presence of two or more risk factors had significant impact on development of cardiotoxicity.

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial.

The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity. Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates. Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6 rs77679196 and CBR3 rs1056892 were significantly associated with congestive heart failure, p < 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab. TRPC6 rs77679196 and CBR3 rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia.

Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. However, biomarkers have been shown to be aberrant prior to any detectable functional or clinical deficit in cardiac function. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients.

Is there a window of opportunity to optimize trastuzumab cardiac monitoring?

BACKGROUNDIt remains unclear whether the current arbitrary screening recommendations of trastuzumab-related cardiotoxicity provides an adequate balance between preventing heart damage and curtailing a curative treatment.AIMTo determine the incidence rate and consequences of trastuzumab-induced cardiotoxicity as adjuvant treatment in a real-world scenario.METHODSWe present a retrospective analysis of cardiac function measured by echocardiogram at baseline and every 3 mo during trastuzumab treatment. Cardiotoxicity was defined as a drop in left ventricular ejection fraction (LVEF) ≥ 10% from baseline and/or any drop < 50%. RESULTSBetween January 2011 and December 2014, 407 patients were selected. Most (93.6%) were treated with an anthracycline followed by a taxane-based regimen and trastuzumab for 12 mo. Forty patients (9.8%) had cardiotoxicity. None of them were symptomatic, and 28 (72.5%) completely recovered LVEF. Cardiotoxicity happened early as shown by LVEF measured on echocardiogram 2 to 4 as compared to 5 to 7 (odds ratio = 2.47, 95% confidence interval: 1.09, 5.63, P = 0.024). There were 54 deaths (13.3%) during the 70-mo follow-up period; 1 (0.2%) was attributed to late cardiotoxicity (4 years after treatment). The absence of symptomatic cardiotoxicity during trastuzumab treatment and moreover the early occurrence on the treatment period may translate into a strategy to evaluate less frequently.CONCLUSIONWe observed a 10% rate of asymptomatic cardiotoxicity, which mirrors the results from the large adjuvant trials. Despite being transient, an LVEF drop led to frequent treatment delays and interruptions. It remains unclear whether LVEF decline is predictive of late cardiotoxicity, and treatment efficacy is compromised.

Prevention of trastuzumab-related cardiotoxicity in HER-2 positive breast cancer patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Trastuzumab (TZ) is a key therapy for HER-2 positive breast cancer that may have different side effects on the cardiovascular system. One of the most concerning complications is cancer therapy-related cardiac dysfunction (CTRCD). In literature there are conflicting data about the efficacy of heart failure drugs like ACE-inhibitors, ARBs and beta-blockers to prevent such an event. Purpose Aim of this study is to describe our experience on cardioprotective drugs in preventing TZ-related CTRCD. Methods 105 consecutive women affected by HER-2 positive breast cancer treated with TZ referring to our echo-lab were enrolled in our single center prospective study. 3 patients were excluded due to an early TZ suspension not related to cardiovascular complications. Thus 102 patients (97,1%) were eligible for analyses. 86 of these (84,3%) were also treated with Anthracyclines. All patients underwent consecutive transthoracic echocardiography (TTE) before starting TZ and then every 3 months up to 12 months. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software. A complete clinical evaluation was also performed at each follow up. LV systolic dysfunction was defined as an absolute reduction of LVEF &amp;gt;10% from baseline to LVEF &amp;lt; 53% or a relative reduction of GLS &amp;gt;15% from baseline and a reduction of LVEF &amp;gt;10% from baseline. Results Overall, before starting TZ, 12 patients were taking ACE-inhibitors or ARBs (11,8%) and 5 patients beta-blockers (4,9%). CTRCD occurred in 11 patients (10,8%), among these 9 (81,8%) weren’t taking any heart failure drugs and 5 (45,5%) didn’t present any cardiovascular risk factor. We observed no significant association among cardiovascular risk factors. Use of potential cardioprotective drugs before TZ administration seems to reduce the risk of development of myocardial dysfunction (relative risk 1,67; 95% confidence interval [CI], 0,41 to 6,82; P &amp;gt; 0.05). No clear association was found between any cardiovascular risk factors and CTRCD (relative risk 0,81; 95% confidence interval [CI], 0,26 to 2,47; P &amp;gt; 0.05). Conclusions In HER-2 positive breast cancer patients treated with TZ an early treatment with ACE-inhibitors or ARBs and/or beta-blockers is associated to the prevention of CTRCD. CTRCD seems not to be related to the presence of cardiovascular risk factors. Abstract Figure. Baseline patient characteristics

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan

Abstract Aims Despite being an essential therapy for breast cancer, trastuzumab has potential risks of cardiotoxicity. The incidence of trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) and its predictors remain unknown in Taiwan. Methods and results Through a three-hospital retrospective cohort study, we analyzed the incidence of MACCE in 386 breast cancer patients exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab nonusers, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4% and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67% and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than nonusers. Conclusions From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, National Cheng Kung University Hospital

Immediate evaluation of global longitudinal strain at initiation of trastuzumab treatment in breast cancer patients.

Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. Since the possibility to detect signs of acute myocardial deterioration at treatment initiation is not clarified, the objective of this study was to assess changes in GLS and biomarkers within the first 2weeks of trastuzumab treatment. In a prospective cohort study, 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8%, GLS -19.9%, 40% hypertension) scheduled for trastuzumab treatment were included. Echocardiography and measurement of troponin and NT-proBrain-Natriuretic-Peptide were conducted before initiation of trastuzumab, at days 3, 7, and 14 and after 3, 6, and 9 months. A significant deterioration in LVEF from 62.8% (SD±3.6) to 58.4% (SD±4.1) (p<0.0001), GLS from -19.9 (SD±2.1) to -18.1 (SD±2.5) (p=0.004), s' (p<0.0001), e' septal (p=0.008), and s' RV (p<0.0001) occurred at 9 months and was preceded by significant changes in these parameters within the first 14 days. After 14 days, 12 patients (27%) had a ≥10% deterioration in GLS, which was associated with significantly lower LVEF at 55.2% (SD±4.1) at 9months compared to patients with<10% early deterioration in GLS (LVEF=59.5% (SD±3.5) (p=0.001)). No difference in plasma concentrations of biomarkers was observed between the two groups. In this study deteriorations in key echocardiographic parameters within normal limits were detected during the first 2weeks of trastuzumab treatment, and an early ≥10% deterioration in GLS was associated with a lower LVEF at 9months.

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan.

AimsIn contrast to Western patients with breast cancer, Asian patients are relatively younger at diagnosis, and most are free from traditional cardiovascular risk factors. Despite trastuzumab‐related major adverse cardiac and cerebrovascular event (MACCE) being reported, its incidence and predictors remain unknown in Taiwan.Methods and resultsThrough a three‐hospital retrospective cohort study, we analysed the incidence of MACCE in 386 breast cancer patients' exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13 502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab non‐users, the incidence of MACCE was measured with a median follow‐up of 36 months. In the hospital‐based study, among 386 patients receiving trastuzumab, the 5‐year incidences of MACCE and heart failure (HF) were 5.4 and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67 and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than non‐users.ConclusionsFrom clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.

Successful Use of Digoxin for Trastuzumab-related Cardiotoxicity to Facilitate Breast Surgery in a Patient with Metastatic Breast Cancer

Successful Use of Digoxin for Trastuzumab-related Cardiotoxicity to Facilitate Breast Surgery in a Patient with Metastatic Breast Cancer

Does trastuzumab-related cardiotoxicity influence long-term outcome in patients with HER-2 positive breast cancer? A prospective study

IntroductionTrastuzumab is a monoclonal antibody directed against the HER-2 receptor that has led, in an adjuvant setting, to higher disease-free (DFS) and overall survival (OS) in HER-2 positive breast cancer (BC) compared with chemotherapy alone. Cardiotoxicity often results in early discontinuation of trastuzumab, which may elevate the risk of cancer recurrence or mortality. Our study aimed to assess how early interruption or early permanent termination of adjuvant trastuzumab treatment influences DFS and OS of patients with HER-2 positive BC.Material and methodsThis is a prospective observation of 253 women (55 ±10 years of age) with HER-2 positive unilateral, non-metastatic BC treated with trastuzumab in an adjuvant setting. To monitor the safety of the treatment echocardiography was performed at baseline and every 3 months up to 12 months after the end of therapy. If cardiotoxicity developed, trastuzumab was stopped early. Overall survival and DFS were assessed.ResultsTrastuzumab-associated cardiac complications resulting in treatment discontinuation developed in 52 (20.55%) patients. Median DFS time was 21.1 months in the group with interruption compared with 25.7 months in the group with full trastuzumab treatment, being significantly shorter (HR = 2.32, 95% CI: 1.15–4.71, p = 0.0106). Two year OS in the interruption and no-interruption groups were 80.8% and 88.5%, respectively, which were not statistically significantly different (p = 0.268). In a multivariate regression analysis the cumulative dose of anthracycline (OR = 1.01, 95% CI: 1.00–1.01, p = 0.002) and LVEF at baseline (OR = 0.83, 95% CI: 0.70–0.99, p = 0.0344) were independent predictors of a cardiotoxic effect.ConclusionsTrastuzumab-related cardiotoxicity resulting in early treatment discontinuation negatively influences DFS, but does not seem to influence OS.

Deceleration capacity of heart rate predicts trastuzumab-related cardiotoxicity in patients with HER2-positive breast cancer: A prospective observational study.

Trastuzumab is the standard choice for anti-human epidermal growth factor receptor 2 (HER2) therapy. Cardiotoxicity is one of the main adverse effects of trastuzumab. How to early predict trastuzumab-related cardiotoxicity remains a significant problem in clinical practice. The deceleration capacity of the heart rate (DC) has been shown to be a powerful predictor of adverse outcomes in various heart diseases. In the study, the role of DC in early predicting trastuzumab-related cardiotoxicity was investigated. A total of 150 patients were prospectively investigated the clinical value of the DC in predicting trastuzumab-related cardiotoxicity in patients with HER2-positive breast cancer treated with trastuzumab at Guangxi Medical University Cancer Hospital from June 2015 to June 2017. DC, mean heart rate and heart rate variability (HRV) indices, including the standard deviation of all normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD), were assessed before treatment, and the left ventricular ejection fraction (LVEF) was regularly monitored for 2years (before, during and after treatment) to evaluate cardiotoxicity. Among 150 eligible patients, 28 (18.7%) developed cardiotoxicity. Patients with cardiotoxicity were older (P<.05), higher anthracycline dose (P<.001) and had lower RMSSD (P<.05), SDNN, DC and baseline LVEF (P<.001), than patients without cardiotoxicity. Logistic regression analysis revealed lower DC, lower baseline LVEF and higher anthracycline dose were independent risk factors of trastuzumab-related cardiotoxicity. Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for DC than for the baseline LVEF in predicting cardiotoxicity (0.88 vs 0.77, P=.032). Additionally, DC had higher sensitivity (78.6% vs 67.9%) and specificity (83.6% vs 77.9%) in predicting cardiotoxicity than the baseline LVEF. Linear regression analysis showed among patients who developed cardiotoxicity, lower DC was associated with an earlier onset (P<.01). The present study found that DC was a stronger predictor of trastuzumab-related cardiotoxicity development than the baseline LVEF and HRV. Linear regression analysis showed among patients who developed cardiotoxicity, lower DC was associated with an earlier onset. DC should be a potential clinical indicator for the early prediction of trastuzumab-related cardiotoxicity.

229P Can immunogloblun -/+ steroid treatment protect trastuzumab cardiotoxicity, a rabbit model trial

Cardiotoxicity (CTX) remains a clinically significant side effect of anti-HER2 therapies. Trastuzumab-related cardiotoxicity is most often manifested by an asymptomatic decrease in left ventricular ejection fraction (LVEF) and less often by clinical heart failure. The aim of this study is to demonstrate the trastuzumab cardiotoxicity with cardiac marker changing and efficacy of steroid and intravenous immunoglobulin (ivig) therapy in the prevention of cardiotoxicity.

Trastuzumab-Related Cardiotoxicity and Cardiac Care in Patients With HER2 Positive Metastatic Breast Cancer

Prolonged trastuzumab therapy is the standard of care for women with metastatic HER2 positive (HER2+) breast cancer. There are limited data on the incidence of cardiotoxicity, its treatment implication, and cardiac care in these patients. We retrospectively identified consecutive women who received >12 months of trastuzumab treatment at Princess Margaret Cancer Centre (Toronto, ON) from 2007 to 2012 for metastatic HER2 positive breast cancer and followed them until death or August 2018. Patients were included if a pretherapy multigated acquisition scan and ≥2 subsequent follow-up scans were available. The Cardiac Review and Evaluation Committee Criteria were used to identify cardiotoxicity. Baseline characteristics and outcomes (final left ventricular ejection fraction, change in LVEF, trastuzumab interruption) were compared in patients with and without cardiotoxicity. Cardiac care and treatment received were recorded. Sixty patients (mean age 52 ± 10.4 years) were included. The median trastuzumab exposure was 37 cycles (interquartile range 23 to 56) over 28 months (interquartile range 19 to 49) and 48% received previous anthracycline therapy. The cumulative incidence of cardiotoxicity was 35% (95% CI 23 to 48) at 3 years. Patients who developed cardiotoxicity were more likely to receive third-line cancer treatments and had lower final LVEF than patients without (54.9% ± 6.3% vs 64% ± 4.9%, p <0.001). Of the 23 patients with cardiotoxicity, 10 (43%) had trastuzumab interrupted for at least 1 cycle, only 7 (30%) patients were seen by a cardiologist and 4 (17%) received cardiac medications. In conclusion, patients with metastatic breast cancer receiving prolonged trastuzumab therapy appear to have high rates of cardiotoxicity. This was associated with high rates of trastuzumab interruption, but low rates of cardiology referral and cardiac treatment, reflecting a potential cardiac care gap.

P1533 Early evaluation of global longitudinal strain and biomarkers at initiation of trastuzumab treatment in breast cancer patients

Abstract Funding Acknowledgements The Danish Heart Foundation, Copenhagen (grant number: 14-R97-A5188-22839 and 15-R99-A5940). The Research Fond of the Region of Southern Denmark. Background Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. The possibility to detect signs of acute myocardial deterioration at treatment initiation is not thoroughly investigated. Accordingly, the aim of this study was to assess changes in GLS and biomarkers within the first two weeks of trastuzumab treatment. Methods In a prospective cohort study 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8% (SD ± 3.6), GLS -19.9% (SD ± 2.1), 40% hypertension) were included. Examinations including echocardiography and measurement of troponin T and NT-proBrain Natriuretic Peptide were conducted before initiation of trastuzumab, at day 3, 7 and 14 and after 3, 6 and 9 months. Results A significant deterioration in LVEF, GLS, s’, e’ septal and s’RV occurred during the 9 months study period and was proceed by significant changes in all these parameters within the first 14 days. After 14 days 12 patients (27%) had an increase in GLS ≥10 %, which was associated with significantly lower LVEF at nine month at 55.2% (SD ± 4.1) vs. 59.5% (SD ± 3.5) (p = 0.001) compared to patients with &amp;lt;10 % early increase in GLS (Figure 1). No difference in plasma concentrations of cardiac biomarkers was observed between the two groups. Conclusion In this cohort study deteriorations in key echocardiographic parameters were detected within the first two weeks of trastuzumab treatment, and an early 10 % increase in GLS was associated with a lower LVEF at nine months. Abstract P1533 Figure 1

Reversibility of trastuzumab induced cardiotoxicity in breast cancer patients: A prospective observational study

Trastuzumab has led to a significant improvement in the treatment of both advanced and early breast cancer that over-expresses HER2 receptors. However, it is associated with an important cardiotoxicity that requires a systematic monitoring of left ventricular ejection fraction (LVEF) before and during the treatment. We present our experience with patients who developed trastuzumab-related cardiotoxicity. To evaluate the incidence and the reversibility of trastuzumab induced cardiotoxicity (TIC) in our cardio-oncology unit. We conducted a prospective observational study from January 2017 to november 2018 in the cardio-oncology unit of Casablanca, Morocco. In total, 973 patients were included. The average LVEF before initiation of trastuzumab was 59.9 ± 11.2% and 51.9 ± 6.6% at the end of treatment. A decreased LVEF was detected in 38 patients (3.9%), symptomatic in 20 cases, asymptomatic in 18 patients. TIC occured for a mean cumulative dose > 40 mg/m 2 . During the follow-up, 32 patients (84.2%) had a retrieval of their LVEF after a mean period of 6.4 months after trastuzumab termination. 6 cases of TIC were irreversible despite an optimal cardioprotective therapy. Patients who develop TIC generally improve their LVEF on removal of the agent and after initiation of cardioprotective therapy. The clinical outcome is more favorable than anthracycline cardiotoxicity. This reversibility is usually observed in early identified patients, showing the importance of a systematic monitoring of LV function before, during and after the treatment.

Cardiotoxicity Alerts during Treatment with Trastuzumab in Breast Cancer at Four-year Follow-up

Background: Adjuvant treatment of HER2+ breast cancer includes adriamycin and trastuzumab, a monoclonal antibody that producescardiotoxicity. The actual epidemiologic impact of trastuzumab-related cardiotoxicity in unselected populations in Argentinaremains unknown.Objectives: The aim of this study was to evaluate the impact of trastuzumab-related cardiotoxicity during adjuvant treatment forbreast cancer in an unselected population after >12 months of completing therapy.Methods: Among 888 patients prospectively evaluated for breast cancer, 231 (38%) were HER2+ and received adjuvant therapy withadriamycin and trastuzumab. Left ventricular ejection fraction was evaluated before treatment, after completing adriamycin and thenevery 3 months during follow-up. Cardiotoxicity was defined as a decline in left ventricular ejection fraction >10%, according to the definitionof the American College of Cardiology and was compared with the definitions of the B-31 trial and the MD Anderson Cancer Center.Results: A decline in left ventricular ejection fraction >10% from baseline values occurred in 65% (n=150) of the patients during amean follow-up of 48±12 months. In the per group analysis, patients included in the B-31and MD Anderson Cancer Center vs. theAmerican College of Cardiology definitions presented greater percent fall in left ventricular ejection fraction during treatment: 20%vs. 20% vs. 16%, respectively (p <0.04) and ended treatment with left ventricular ejection fraction <50% in 42% vs. 41% vs. 33% ofcases, respectively (p=0.01).Conclusions: In the population treated with trastuzumab under cardio-oncology surveillance during 48±12 months:1- Left ventricular ejection fraction was significantly decreased in more than 60% of patients.2- Different guidelines show different cardiotoxicity risks which demands continuous cardio-oncological monitoring.

Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity

ObjectivesThe aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC). BackgroundCardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results. MethodsA total of 222 patients with early-stage human epidermal growth factor receptor 2–positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure; cardiac death, arrhythmia, or infarction; a decrease in LVEF of >15% from baseline; or a decrease in LVEF of >10% to <50%. ResultsTRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p < 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a “low-risk TRC score” to identify patients with low TRC incidence. ConclusionsLow baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS]; NCT00858039)

Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors.

Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors.

Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer.

Clinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab. In this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment-related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest. Of the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08). The combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment-related cardiotoxicity. Patients with bca experiencing cancer treatment-related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.