Safety of trastuzumab in women with HER2+ breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12522-e12522
Author(s):  
Somaira Nowsheen ◽  
Khaled Aziz ◽  
Jae Yoon Park ◽  
Hector R. Villarraga ◽  
Joerg Herrmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Function ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Physical Symptoms ◽  
Left Ventricular ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
History Of ◽  
Normal Lvef

e12522 Background: Trastuzumab is widely used in management of HER2+ breast cancer patients. A known adverse effect of trastuzumab use is cardiac dysfunction, which can often be reversed with cessation of therapy. Our objectives were to 1) assess if trastuzumab can be safely administered to breast cancer patients with reduced cardiac function and 2) identify patient characteristics that predict susceptibility to trastuzumab-induced cardiac dysfunction. Methods: A retrospective analysis was performed on female patients seen at Mayo Clinic for HER2+ breast cancer and treated with trastuzumab for localized or metastatic disease between January 1, 2000 and August 31, 2015. Eligibility criteria included documentation of and results from at least one echocardiogram prior to and at least one after trastuzumab initiation. Left ventricular (LV) ejection fraction (EF) of 53% or more was considered normal. Any LVEF reduction of 10% or more was considered significant. Among patients with normal EF, age strata of < 45, 45-60, and > 60 at time of trastuzumab initiation were used to assess risk factors for clinically diagnosed cardiac dysfunction (defined as EF < 53 or abnormal strain and physical symptoms of heart failure (HF)). Results: We identified 335 women (mean age 53.3, with 25.3% age < 45, 44.5% age 45-60, and 30.1% age > 60) who had normal LVEF (median EF 64, range: 53-75) and 23 women (mean age 53.4, with 30.4% age < 45, 43.5% age 45-60, and 26.1% age > 60) who had low LVEF at baseline (median EF 52, range: 25-52). Approximately a third (34.3%) of women with normal LVEF prior to initiation of therapy had at least one subsequent echocardiogram showing a drop of 10% or a low LVEF ( < 53). Approximately a quarter (26%) of women with low LVEF at baseline had a 10% drop in LVEF. HF incidence increased with age. Predictive factors for trastuzumab-induced cardiac dysfunction were obesity and history of coronary artery disease (CAD) across all age strata, and chest irradiation (IR) for those aged 45-60 only. Conclusions: Our results suggest that trastuzumab can be administered in women with reduced cardiac function at no greater risk than in those with preserved cardiac function. Some women with no obesity, history of CAD, or history of chest IR may not need echocardiograms during trastuzumab therapy.

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.

scholarly journals Electrocardiographic evaluation of depolarization and repolarization abnormalities in breast cancer patients with HER2-inhibitor related cardiac dysfunction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Kinoshita ◽  
H Yuzawa ◽  
R Wada ◽  
K Yano ◽  
S Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Control Group ◽  
Case Group ◽  
Breast Cancer Patients ◽  
T Wave ◽  
And Control ◽  
Repolarization Abnormalities

Abstract Background The arrhythmic substrates of the myocardium such as depolarization and repolarization abnormalities are thought to reflect cardiac dysfunction prior to the morphologic left ventricular dysfunction. Activation time (AT), recovery time (RT) and T wave peek-end interval dispersion (Tpe-dispersion) are useful indicators of the arrhythmic substrate. We examined the appearance of depolarization and repolarization abnormalities in patients with cancer therapeutics-related cardiac dysfunction (CTRCD) using AT, RT and Tpe-dispersion. Methods We conducted a standardized case-control study of CTRCD with 40 patients who developed breast cancer and treated with trastuzumab (13 cases and 27 controls). We assessed the relation between electrocardiographic indexes, including AT, RT and corrected Tpe-dispersion, and CTRCD. QT intervals were measured by Fridericia method, and QT observer 3 software were used for the measurement of all electrocardiographic indexes. Results LVEF in case and control group were 45.7±8% and 69.2±6%, respectively. AT in aVR lead was significantly higher in case group compared with control (28.8±7ms vs 22.8±5ms, P=0.02). corrected Tpe-dispersion tended to be higher in case group than that of control group (43.2±19ms vs 31.9±10ms, P=0.06). QT dispersion and RT dispersion were not different between case and control group. Conclusions Our study demonstrated that AT in aVR may predict cardiac dysfunction in breast cancer patients with HER2-inhibitor related cardiac dysfunction. More detailed studies using other modalities which can detect depolarization and repolarization abnormalities, including ventricular late potentials and T wave alternans, are needed. Funding Acknowledgement Type of funding source: None

scholarly journals Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Yamashita ◽  
H Tanaka ◽  
K Hatazawa ◽  
Y Tanaka ◽  
K Sumimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Previous History ◽  
Left Ventricular ◽  
Clinical Risk Factors ◽  
Lv Function ◽  
Breast Cancer Patients ◽  
Clinical Risk ◽  
History Of

Abstract Background The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity following treatment with chemotherapy. However, the association between clinical risk factors and left ventricular (LV) function in breast cancer patients is currently unclear. Purpose Our purpose was to investigate the impact of baseline risk factors on LV function in patients with preserved LV ejection fraction (LVEF) who have undergone anthracycline or trastuzumab chemotherapy for breast cancer. Methods We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59±13 years and LVEF was 67±5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of &gt;10% to an absolute value of &lt;53% after chemotherapy. Based on the 2016 ESC position paper, clinical risk factors for CTRCD were defined as: (1) a cumulative total doxorubicin dose of ≥240 mg/m2, (2) age ≥65-year-old, (3) body mass index ≥30 kg/m2, (4) a previous history of radiation therapy to chest or mediastinum, (5) B-type natriuretic peptide ≥100pg/mL, (6) a previous history of cardiovascular disease, (7) atrial fibrillation, (8) hypertension, (9) diabetes mellitus, (10) current or ex-smoker. Results The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (−9.3±10.8% vs. −2.2±10.2%; p=0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p=0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3±29.0 g/m2 vs. 83.2±21.0g /m2, p&lt;0.001), lower global longitudinal strain (18.4±2.8% vs. 20.0±2.6%, p=0.06) and higher E/e' (10.4 (8.9–13.0) vs. 9.0 (7.4–10.9), p=0.06) compared to those without. Conclusions Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy. Funding Acknowledgement Type of funding source: None

scholarly journals Assessment of Survival and Cardiotoxicity of Adjuvant Trastuzumab among HER2 Breast Cancer Patients in an Oncology Centre in Malaysia

2018 ◽  
Vol 3 (1) ◽  
pp. 33
Author(s):  
Harissa Husainy Hasbullah ◽  
Anita Bustamam ◽  
Tho Lye Munn ◽  
Vincent Phua
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer

Introduction: Adjuvant trastuzumab has been used in human epidermal growth factor-2 (HER2) breast cancer to improve survival but with concern of cardiotoxicity. Our study is the first to review efficacy and toxicity of adjuvant trastuzumab in Malaysia. Methods: This is a retrospective cohort study on HER2 non metastatic breast cancer patients in University Malaya Medical Centre diagnosed between October 2006 and May 2011. Two cohorts were created based on whether or not they received adjuvant trastuzumab. Disease free survival (DFS) and overall survival (OS) for both groups were estimated using Kaplan Meier method and compared using Log rank test. Cox proportional hazards regression models analysed for potential covariates of age, tumour size and grade, node and estrogen receptor (ER) status. Trastuzumab cardiotoxicity was defined as left ventricular systolic dysfunction or heart failure with or without symptoms and graded using Common Terminology Criteria for Adverse Events (CTCAE 4.0). Results: 170 HER2 non metastatic breast cancer patients were identified. Thirty-three received trastuzumab and 136 did not. Median age was 53.4 ± 10.3 years old. Significantly more ER negative patients received trastuzumab. Four years DFS in ‘trastuzumab’ versus ‘no trastuzumab’ cohort was 90.9% vs 74.5% (p = 0.027). Four years OS was 91% vs 84.7% (p = 0.30) respectively. Majority tolerated trastuzumab with no toxicity. Five patients (15.2%) experienced cardiotoxicity (all grade I).Conclusions: Adjuvant trastuzumab significantly improved DFS in HER2 breast cancer. Treatment was well tolerated. With this we propose the justification for adjuvant trastuzumab in HER2 breast cancer in our population.

scholarly journals Prognostic Factors for Cancer Therapeutics-Related Cardiac Dysfunction in Breast Cancer Patients Treated with Current Anthracycline Regimens

2021 ◽  
Author(s):  
Koichi Egashira ◽  
Daisuke Sueta ◽  
Mai Tomiguchi ◽  
Kaori Hidaka ◽  
Lisa Goto-Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Cumulative Dose ◽  
Cardiac Dysfunction ◽  
Cancer Therapeutics ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction

Abstract Background Anthracycline therapies cause myocardial damage and the onset of heart failure, depending on their doses. We investigated prognostic factors for cancer therapeutics-related cardiac dysfunction (CTRCD) in patients receiving modern anthracycline therapies. Methods Of 472 breast cancer patients with complete data treated with anthracycline, 8 were diagnosed with CTRCD. Results Multivariate regression analyses revealed that the anthracycline cumulative dose, concomitant use of molecular targeted drugs and a prechemotherapy left ventricular ejection fraction < 50% were independent and significant predictors of the onset of CTRCD. Conclusions Even in the modern era, the anthracycline cumulative dose is an independent risk factor for the onset of CTRCD.

Cardiac troponin T for early detection of cardiotoxicity in breast cancer patients treated with epirubicin

Open Medicine ◽  
2009 ◽  
Vol 4 (3) ◽  
pp. 327-330
Author(s):  
Refik Erdim ◽  
Aydin Celiker ◽  
Gökmen Gemici ◽  
Sena Tokay ◽  
Gözde Ülfer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Elevated Serum ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
One Year

AbstractThe aim of the study was to investigate the role of cTnT for the prediction of long term cardiac dysfunction after epirubicin-containing adjuvant chemotherapy for breast cancer. The study group comprised of 45 patients (all female; mean age 48 ±8 years), treated with epirubicin-containing adjuvant chemotherapy for stage 2 and stage 3 breast cancer. Patients received either 4 cycles of cyclophosphamide plus epirubicin (90 mg/m2) (n=23; stage 2 breast cancer) or 6 cycles of cyclophosphamide plus epirubicin (75 mg/m2) plus fluorouracil (n=18; stage 3 breast cancer). Venous blood samples were drawn, before and 72 hours after, every cycle of chemotherapy for the measurement of cTnT. Cardiac assessment was carried out at baseline and 1 year after chemotherapy by clinical evaluation, electrocardiography, radio-nuclide ventriculography (RNV) and transthoracic echocardiography. All patients remained free of clinical heart failure during the study period. In 26 patients (63%), cTnT was elevated after chemotherapy. Mean left ventricular ejection fraction, assessed by RNV at baseline and one year after chemotherapy, were 61±8% and 56±7% (p<0.0001). The sensitivity and specifity of cTnT for the detection of left ventricular systolic dysfunction at one year were 69% and 39% respectively. Echocardiographic examinations at baseline and one year after chemotherapy revealed a significant decrease in E/A ratio from 1.15±0.3 to 0.9±0.2 in cTnT positive patients, suggesting diastolic dysfunction. In conclusion, elevated serum cTnT levels after epirubicin-containing adjuvant chemotherapy for stage 2 and stage 3 breast cancer, predict future cardiac dysfunction with moderate sensitivity and poor specificity.

scholarly journals Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
K Yamashita ◽  
H Tanaka ◽  
K Hatazawa ◽  
Y Tanaka ◽  
A Shono ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Previous History ◽  
Left Ventricular ◽  
Clinical Risk Factors ◽  
Breast Cancer Patients ◽  
Clinical Risk ◽  
Lv Dysfunction ◽  
History Of

Abstract Funding Acknowledgements Type of funding sources: None. Background The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity. Purpose Our purpose was to investigate the impact of baseline risk factors on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF) who have undergone chemotherapy for breast cancer. Methods We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59 ± 13 years and LVEF was 67 ± 5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of &gt;10% to an absolute value of &lt;53% after chemotherapy. Based on the 2016 ESC position paper, clinical risk factors for CTRCD were defined as: (1) a cumulative total doxorubicin dose of ≥ 240mg/m², (2) age ≥ 65-year-old, (3) body mass index ≥ 30kg/m², (4) a previous history of radiation therapy to chest or mediastinum, (5) B-type natriuretic peptide ≥ 100pg/mL, (6) a previous history of cardiovascular disease, (7) atrial fibrillation, (8) hypertension, (9) diabetes mellitus, (10) current or ex-smoker. Results The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (-9.3 ± 10.8% vs. -2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p = 0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3 ± 29.0g/m² vs. 83.2 ± 21.0g/m², p &lt; 0.001), lower global longitudinal strain (18.4 ± 2.8% vs. 20.0 ± 2.6%, p = 0.06) and higher E/e’ (10.4 (8.9-13.0) vs. 9.0 (7.4-10.9), p = 0.06) compared to those without.  Furthermore, receiver-operator characteristics curve analysis showed that an optimal cut off value of a cumulative total doxorubicin dose for developing LV dysfunction in patients with more than any of four risk factors was lower than that in those without (180 mg/m² vs. 280 mg/m²). Conclusions Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy. Abstract Figure.

Role of neutrophils in the early presymptomatic stages of doxorubicin cardiotoxicity in breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 98-98
Author(s):  
Valentina K Todorova ◽  
Marjorie L Beggs ◽  
Eric R Siegel ◽  
Issam Makhoul ◽  
Jeanne Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Function ◽  
Cancer Patients ◽  
Preliminary Finding ◽  
Cathepsin G ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Early Stages ◽  
Preventive Medication ◽  
Normal Lvef

98 Background: Doxorubicin (DOX) cardiotoxicity is cumulative-dose-dependent and begins with the first dose of chemotherapy. No biomarker for early presymptomatic detection of DOX cardiotoxicity has been validated. Our preliminary microarray-based study on DOX cardiotoxicity of breast cancer patients showed that neutrophil-associated inflammation was partly responsible for this side effect of DOX Based on our preliminary finding, the aim of this study was to examine the expression of the top dysregulated neutrophil-specific genes, including alpha-defensins, arginase, cathepsin G, elastase, haptoglobin, metalloprotease 9, cathelicidin 8 in the peripheral blood mononuclear cells (PBMCs) of breast cancer patients treated with DOX-based chemotherapy. Methods: Blood samples of 15 women treated for breast cancer with DOX-based chemotherapy were collected before the start and after the 1st cycle of chemotherapy. Cardiac function was assessed before the start and after the completion of chemotherapy. A decrease of left ventricle ejection fraction (LVEF) > 10% or < 55% was considered abnormal. PBMC gene expressions of the target genes were assessed by quantitative RT-PCR and normalized to 18S. Data were analyzed using 2-deltadelta CT method and compared between patients with abnormal versus those with normal LVEF. Results: A single dose of DOX-based chemotherapy induced significantly greater mRNA levels of the examined genes in PBMC of patients with subsequent abnormal decline of LVEF (n = 5) versus those patients who maintained a normal LVEF. The elevated neutrophil-associated transcripts in the early stages of DOX-based chemotherapy were independent of the neutrophil count. Conclusions: We have identified a set of transcripts in the early stages of DOX-based chemotherapy that can serve as biomarkers for prediction of later impairment of cardiac function in breast cancer patients. Biomarkers for early prediction of DOX-induced cardiotoxicity could allow individualization of chemotherapy and/or testing the effectiveness of cardio-preventive medication, and ultimately will help to reduce the incidence of the cardiotoxicity-associated morbidity and mortality in cancer survivors.

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