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.

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 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.

Prospective Evaluation of Early Cardiac Damage Induced by Epirubicin-Containing Adjuvant Chemotherapy and Locoregional Radiotherapy in Breast Cancer Patients

2001 ◽  
Vol 19 (10) ◽  
pp. 2746-2753 ◽  
Author(s):  
M.T. Meinardi ◽  
D.J. van Veldhuisen ◽  
J.A. Gietema ◽  
W.V. Dolsma ◽  
F. Boomsma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Diastolic Function ◽  
Cancer Patients ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Group I

PURPOSE: To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS: Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction. RESULTS: No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P = .001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P < .01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P = .04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P < .01). No persistent alterations were found in diastolic function and HRV. CONCLUSION: Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.

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.

Cardiotoxicity risks of adjuvant trastuzumab in Asian breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 561-561
Author(s):  
V. Shih ◽  
A. Chan ◽  
J. Chiang ◽  
C. Teo ◽  
J. Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction ◽  
Chi Square Test

561 Background: Adjuvant trastuzumab (T)-based chemotherapy has been shown to reduce relapse and improve survival in breast cancer patients but has been associated with increased risks of cardiotoxicity. Our study aims to define the incidence and severity of cardiotoxicity amongst Asian breast cancer patients. Methods: This is a retrospective review of patients who have received adjuvant T from June 2005 to 2007. Cardiotoxicity was defined as a drop in left ventricular ejection fraction (LVEF) to less than 50% and/or reduction of > 10% of baseline. Cardiovascular (CVS) risk factors were defined as having a family history or presence of CAD, hypertension, diabetes mellitus, hyperlipidemia and smoking. We used pair sampled t-test to evaluate the mean LVEF change and Chi-square test to evaluate the association of cardiotoxicity and demographics. Results: There were 179 female patients. Cardiotoxicity was reported in 70 (39.1%), of whom 59 had asymptomatic decline in LVEF and 11 experienced CHF. Mean LVEF, comparing various time points (3, 6, 9 and 12 months) against baseline showed statistically significant decline (p<0.05). T was withheld (n=33) due to asymptomatic decline in LVEF (n=24), symptomatic heart failure (n=4) and both (n=5). Twenty-one with resolution of CHF (n=7) or LVEF recovery (n=14) were rechallenged. Cardiotoxicity recurred in 9 - asymptomatic decline in LVEF (n=8) and recurrent CHF (n=1). There were no cardiac-related deaths. Neither patient demographics nor CVS risk factors predicted for cardiotoxicity. Conclusions: This is one of the largest series reported in Asians receiving T. As previously reported, T-induced cardiotoxicity resulted in mostly asymptomatic reversible decline in LVEF. Our incidence of cardiotoxicity appeared higher (39.1%) in Asians and more importantly, almost half of the patients experienced cardiotoxicity upon rechallenge. It would be prudent to explore whether there is any difference in susceptibility to T-induced cardiotoxicity between the different races. [Table: see text] No significant financial relationships to disclose.

Trastuzumab induced cardiotoxicity in HER2-positive metastatic esogastric cancers.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 152-152 ◽  
Author(s):  
Jerome Martin-Babau ◽  
Yves Eusen ◽  
Cedric Verveur ◽  
Fanny Trouboul ◽  
Caroline Cheneau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Cardiovascular Comorbidities

152 Background: Trastuzumab is widely used in Her2 positive metastatic esophageal and gastric cancers along with chemotherapy. Cardiotoxicity of trastuzumab has been described precisely in Her2 positive breast cancers and occurs with asymptomatic lowering of LVEF (Left Ventricular Ejection Fraction) in up to 10% of cases. Esogastric cancer patients are usually older and have more comorbidities than patients followed for breast cancer. Methods: This monocentric retrospective study measured the incidence of symptomatic and asymptomatic cardiotoxicity in patients treated for metastatic esogastric cancers and its potential impact regarding overall survival from October 2009 to September 2015. Patients should receive trastuzumab with chemotherapy during the period of study for treatment of Her2 positive metastatic esogastric cancer as first-line chemotherapy. Results: 27 patients received trastuzumab along with chemotherapy during the period of study. Median age was 62.3 years, sex ratio 21 M/6 W. The median number of cycles of trastuzumab was 5 cycles. The asymptomatic cardiotoxicity rate, defined by a drop of more than 10% of LVEF between the enrollment echocardiogram and the third month treatment echocardiogram, was of 22%. Symptomatic cardiotoxicity was observed in two patients (7.4%), with one cardiac failure and one myocardial infarction, with no associated death. Cardiovascular comorbidities and cardiac irradiation which is recurrent in this indication did not appear as a predictive factor of cardiotoxicity (p = 1). Overall survival of patients was not statistically modified by the occurring of cardiotoxicity even if we noted a trend to better outcome of the patients presenting an asymptomatic LVEF lowering. Conclusions: This study is to our knowledge the first to focus specifically on the cardiotoxicity of trastuzumab in esogastric metastatic Her2 positive cancer in the real world. These patients seem to be at a higher asymptomatic cardiac risk than breast cancer patients. However cardiovascular comorbidities didn’t appear as predictive factors of trastuzumab induced cardiotoxicity and should not prevent patient from benefiting of this treatment.

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