scholarly journals Long-Term Cardiac Safety Analysis of NCCTG N9831 (Alliance) Adjuvant Trastuzumab Trial

2016 ◽  
Vol 34 (6) ◽  
pp. 581-587 ◽  
Author(s):  
Pooja P. Advani ◽  
Karla V. Ballman ◽  
Travis J. Dockter ◽  
Gerardo Colon-Otero ◽  
Edith A. Perez
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cumulative Incidence ◽  
Cardiac Toxicity ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and long-term evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracycline- and taxane-based therapy) continues to have a favorable benefit-risk ratio.

Fluorouracil, Epirubicin, and Cyclophosphamide With Either Docetaxel or Vinorelbine, With or Without Trastuzumab, As Adjuvant Treatments of Breast Cancer: Final Results of the FinHer Trial

2009 ◽  
Vol 27 (34) ◽  
pp. 5685-5692 ◽  
Author(s):  
Heikki Joensuu ◽  
Petri Bono ◽  
Vesa Kataja ◽  
Tuomo Alanko ◽  
Riitta Kokko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Axillary Node ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction

Purpose Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive cancer are unknown. Patients and Methods One thousand ten women with axillary node–positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. Results Women assigned to docetaxel had better distant disease–free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. Conclusion Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.

Predictors of mortality and heart transplantation in patients with Chagas’ cardiomyopathy and ventricular tachycardia treated with implantable cardioverter-defibrillators

EP Europace ◽  
2019 ◽  
Vol 21 (7) ◽  
pp. 1070-1078 ◽  
Author(s):  
Wagner L Gali ◽  
Alvaro V Sarabanda ◽  
José M Baggio ◽  
Eduardo F Silva ◽  
Gustavo G Gomes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Secondary Prevention ◽  
Heart Transplantation ◽  
Primary Outcome ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Risk Of Death

Aims Data on long-term follow-up of patients with Chagas’ heart disease (ChHD) receiving a secondary prevention implantable cardioverter-defibrillator (ICD) are limited and its benefit is controversial. The aim of this study was to evaluate the long-term outcomes of ChHD patients who received a secondary prevention ICD. Methods and results We assessed the outcomes of consecutive ChHD patients referred to our Institution from 2006 to 2014 for a secondary prevention ICD [89 patients; 58 men; mean age 56 ± 11 years; left ventricular ejection fraction (LVEF), 42 ± 12%]. The primary outcome included a composite of death from any cause or heart transplantation. After a mean follow-up of 59 ± 27 months, the primary outcome occurred in 23 patients (5.3% per year). Multivariate analysis showed that LVEF < 35% [hazard ratio (HR) 4.64; P < 0.01] and age ≥ 65 years (HR 3.19; P < 0.01) were independent predictors of the primary outcome. Using these two risk factors, a risk score was developed, and lower- (no risk factors), intermediate- (one risk factor), and higher-risk (two risk factors) groups were recognized with an annual rate of primary outcome of 1.4%, 7.4%, and 20.4%, respectively. A high burden of appropriate ICD therapies (16% per year) and electrical storms were documented, however, ICD interventions did not impact on the primary outcome. Conclusion Among ChHD patients receiving a secondary prevention ICD, older age (≥65 years) and left ventricular dysfunction (LVEF < 35%) portend a poor outcome and were associated with increased risk of death or heart transplantation. Most patients received appropriate ICD therapies, however, ICD interventions did not impact on the primary outcome.

Asymptomatic cardiotoxicity in long-term breast cancer survivors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24084-e24084
Author(s):  
Mohammed Alaeddine Saidi ◽  
Soumeyya Ghomari
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Survivors ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Breast Cancer Survivors ◽  
Left Ventricular ◽  
Left Ventricular Ejection

e24084 Background: Multimodal approach in the adjuvant treatment of early breast cancer has led to a significant number of survivors. However, the combination of these treatments may increase the risk of long-term cardiotoxicity, particularly in the presence of cardiovascular risk factors (CVRF). Methods: We examined cardiac function in patients who had previously been treated for early breast cancer. Echocardiograms were performed at least 2 years after therapy. We measured left ventricular ejection fraction (LVEF) and reported pre-treatment LVEF and all CVRF. The initial Framingham Risk Score (FRS) has been calculated. Asymptomatic cardiotoxicity was defined by decrease of 5% or more in the LVEF value without clinical symptoms of CHF. Doxorubicin, Trastuzumab, Radiotherapy, older age, and CVRF (hypertension (HTN), diabetes, dyslipidemia, obesity, Waist circumference) were evaluated as potential risk factors for the development of cardiotoxicity. All statistical analysis was performed using SPSS version 25.0. Results: A total of 143 breast cancer survivors with a median age of 46 ± 10 years (range: 26-72) underwent Echocardiogram imaging after a median follow-up of 9,22 years (range: 2 - 22). 48 women were postmenopausal at diagnostic. 32,2% were obese. HTN was present in 15%, diabetes in 12%, and dyslipidemia in 12% of patients. ARA-II was the most used treatment of HTN (55%). 11,9% of patients were under statin therapy. FRS was low in 69%, moderate in 22% and high in 9% of patients. 4 patients had received endocrine therapy alone, none of whom developed cardiotoxicity. There was only one case of symptomatic cardiotoxicity. In the remaining 138 women who received multimodal treatment (Anthracyclines:100%, Docetaxel:62,9%, Endocrine therapy:72%, Trastuzumab:7%, Radiotherapy:83,2%), a statistical but non-clinically significant decrease was observed in LVEF (67.7 ± 3.6 to 65.4 ± 5.1, p < 0.001). 39 women (28,3%) developed asymptomatic cardiotoxicity. In multivariate analysis, factors that contributed to decreased LVEF were HTN (p = 0,006), diabetes (p = 0,008) and dyslipidemia (p = 0,03). Conclusions: The use of adjuvant therapy in breast cancer may increase long term cardiotoxicity particularly in survivors with CVRF. Long-term cardiac follow-up is essential in order to initiate cardioprotective therapy at the right time.

Pre-anthracycline left ventricular ejection fraction (LVEF) assessment and long-term cardiovascular (CV) outcomes in adolescent and young adult (AYA) lymphoma survivors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24060-e24060
Author(s):  
Alma Farooque ◽  
Cibele Carroll ◽  
Amye Juliet Tevaarwerk ◽  
Priyanka Avinash Pophali
Keyword(s):  
Risk Factors ◽  
Left Ventricular ◽  
Adolescent And Young Adult ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Late Cardiotoxicity ◽  
Pre Treatment ◽  
Lymphoma Survivors

e24060 Background: Anthracyclines are known to cause long-term cardiotoxicity. There are no specific guidelines for CV screening and follow-up of AYA patients treated with anthracyclines. Pediatric guidelines focus on long-term imaging surveillance, while for adults, LVEF assessment prior to anthracyclines is recommended. Multiple studies have demonstrated LVEF assessment rarely impacts treatment decisions, especially in the absence of CV symptoms/risk factors, adds to unnecessary costs and delays treatment initiation. Our study aimed to determine the pre-treatment LVEF assessment practices in AYA lymphoma patients treated with anthracyclines and its association with long-term cardiotoxicity. Methods: AYA survivors diagnosed with lymphoma > 5 years ago and treated with anthracyclines at age 15-39 years were identified in a retrospective single institution registry. To ensure adequate follow-up, at least 2 follow-up visits during 2015-19 were required. Data abstracted on eligible subjects included documentation of pre-treatment LVEF evaluation, clinical rationale and treatment regimen. CV risk factors and events were collected pre-treatment and during follow-up. Descriptive statistics were used to summarize data. Results: 64/115 (56%) of AYA lymphoma patients underwent pre-treatment LVEF assessment. Rationale for/against LVEF assessment was rarely documented: low CV risk was recorded as rationale for no LVEF assessment in 2 subjects. Among AYAs who underwent pre-treatment LVEF assessment, no significant abnormalities were detected and no changes in subsequent treatment plans were found. During median follow-up of 6.7 (inter-quartile range 5.4-9.5) years, 6/115 (5%) experienced CV events. Only 2 (1.7%) survivors experienced potential anthracycline-related CV events: 1 moderate cardiomyopathy at 9 years, 1 peri-partum cardiomyopathy and atrial fibrillation due to post-radiation SVC occlusion at 15 years post-treatment. Both these AYAs (aged 38 and 31 years at time of CV events) also had other CV risk factors- family history, smoking, obesity, and hyperlipidemia. Four (3.5%) survivors’ experienced CV events (1 sinus tachyarrhythmia, 1 junctional rhythm, 2 acute/asymptomatic drop in LVEF) unrelated to anthracyclines with clear alternative etiology e.g. sepsis/symptom burden. There was no correlation between having pre-treatment LVEF assessment and occurrence of CV events. 13/115 (11.3%) developed new CV risk factors: 4 hypertension, 6 hyperlipidemia, 3 diabetes. Conclusions: Pre-treatment LVEF assessment is done inconsistently in AYA lymphoma patients but does not impact initial treatment or predict late cardiotoxicity. CV events in long-term AYA lymphoma survivors are rare but evaluation of CV risk factors, early detection and management may be more important than focusing on LVEF assessment.

Long-Term Cardiac Follow-Up in Relapse-Free Patients After Six Courses of Fluorouracil, Epirubicin, and Cyclophosphamide, With Either 50 or 100 mg of Epirubicin, As Adjuvant Therapy for Node-Positive Breast Cancer: French Adjuvant Study Group

2004 ◽  
Vol 22 (15) ◽  
pp. 3070-3079 ◽  
Author(s):  
Jacques Bonneterre ◽  
Henri Roché ◽  
Pierre Kerbrat ◽  
Pierre Fumoleau ◽  
Marie-Josèphe Goudier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Study Group ◽  
Concomitant Disease ◽  
Ventricular Ejection Fraction ◽  
Node Positive ◽  
Positive Breast Cancer

Purpose To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FEC 50) or the same regimen with epirubicin 100 mg/m2 (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group–05 trial. Patients and Methods One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. Conclusion After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection.

Adjuvant Weekly Paclitaxel and Trastuzumab for HER2-Positive Breast Cancer without Risk Factors of Cardiotoxicity. Possibility of Omitting Cardiac Monitoring during Treatment.

2020 ◽  
Author(s):  
Toshiro Mizuno ◽  
Akira Tsunoda ◽  
Yasutaka Tono ◽  
Hiroyasu Oda ◽  
Mikiya Ishihara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
High Body Mass Index ◽  
Left Ventricular ◽  
Cardiac Monitoring ◽  
Weekly Paclitaxel ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Ventricular Ejection Fraction

Abstract Background: Although weekly paclitaxel and trastuzumab is generally considered to be less cardiotoxic than an anthracycline regimen, low baseline left ventricular ejection fraction (LVEF) of ≤55%, hypertension, and high body mass index (BMI) have been reported as risk factors for cardiotoxicity. Without these risk factors, the incidence of cardiotoxicity is expected to be minimal. Method: We retrospectively reviewed the medical records of 86 patients with HER2-positive, node-negative breast cancer between February 2012 and December 2018. Patients were selected for this study according to the following criteria: (1) patients were administered weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by trastuzumab; (2) baseline LVEF was 60% or more; (3) echocardiography was performed before, during, and at the end of treatment; (4) no hypertension or well-controlled with medication; and (5) BMI was < 30. We investigated the occurrence of cardiotoxicity. A decline in LVEF was defined as a decrease of 15% or more from baseline, or < 50% decrease in LVEF.Results: A total of 40 patients fulfilled the eligibility criteria. The median age was 55.5 (35 to 72) and median baseline LVEF was 68% (60 to 77). The median number of echocardiograms was five (3-7). Out of 40, trastuzumab were completed in 39. Among the 39 patients, no symptomatic congestive heart failure or asymptomatic LVEF decline was observed. Conclusion: In our study, no cardiotoxicity was observed in paclitaxel and trastuzumab. Assessment of cardiac function during treatment may be simplified in patients without risk factors for cardiotoxicity.

Prevalence of trastuzumab-induced cardiotoxicity in Uruguayan HER2-positive breast cancer patients treated in a real life setting during a 10 year period.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12537-e12537
Author(s):  
Natalia Camejo ◽  
Cecilia Castillo ◽  
Nora Artagaveytia ◽  
Crisitian Etcheverría ◽  
Jessica Ferradaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiac Toxicity ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Chi Square ◽  
Ventricular Ejection Fraction ◽  
Her 2 ◽  
Positive Breast Cancer

e12537 Background: To estimate the prevalence of Trastuzumab (TTZ) induced cardiotoxicity in Uruguayan women diagnosed with early HER – 2 positive breast cancer (BC) over a period of ten years, treated under the financial coverage of the National Resource Fund (FNR). Methods: A prospective descriptive observational study based on the analysis of an anonymized database provided by the FNR of Uruguayan HER-2 positive early BC patients treated with TTZ between 2006 and 2016. Variables analyzed included: age, menopausal status, stage, presence of cardiovascular risk factors, use or not of anthracyclines, left ventricular ejection fraction prior and during treatment, and temporary or permanent suspension of treatment. Statistical analysis was performed using SPSS Statistics version 25. The variables were assessed through the use of measures of central tendency, dispersion, contingency tables and proportions. To analyze the relationship between the different variables, the Chi-Square test of independence was performed. Results: The analysis included 1401 patients diagnosed with HER-2 + stage I to III breast cancer who received adjuvant TTZ. The mean age at diagnosis was 52.45 years. The prevalence of cardiotoxicity in evaluable patients (1065 pts) was 20.3%. The proportion of patients who had symptomatic heart failure was 3% (32 pts) and in those who discontinued treatment for asymptomatic cardiac toxicity managed to resume trastuzumab prevalence was 92.6 %. About 9,7 % (21 pts) of patients had drop of left ventricular ejection fraction (LVEF) below 50%, whilst 10% drop of LVEF below their baseline levels were found in 75% of patients (162 pts) There is significant difference in the risk of cardiotoxicity according to the type of chemotherapy (anthracycline containing vs non-anthracycline based) (Chi-square = 3.9, p-value < 0.005). There was no evidence of a relationship between cardiovascular risk factors and the development of cardiotoxicity as well there was no evidence between sequential or concurrent use of TTZ with chemotherapy. Conclusions: The prevalence of cardiotoxicity in this study was similar to that reported internationally. The majority of patients did not develop cardiac toxicity and those who presented it did so asymptomatically and reversibly.

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.

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