Disease-Free Survival Advantage of Weekly Epirubicin Plus Tamoxifen Versus Tamoxifen Alone As Adjuvant Treatment of Operable, Node-Positive, Elderly Breast Cancer Patients: 6-Year Follow-Up Results of the French Adjuvant Study Group 08 Trial

2004 ◽  
Vol 22 (23) ◽  
pp. 4674-4682 ◽  
Author(s):  
Pierre Fargeot ◽  
Jacques Bonneterre ◽  
Henri Roché ◽  
Alain Lortholary ◽  
Mario Campone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Node Positive ◽  
Grade 3 ◽  
Disease Free

Purpose To assess whether an epirubicin (EPI) -based chemotherapy plus hormonal regimen improves disease-free (DFS) in women older than 65 years, with node-positive, operable breast cancer (BC), relative to tamoxifen (TAM) alone. Patients and Methods A total of 338 patients were randomly assigned after surgery to receive TAM 30 mg/d for 3 years (TAM, n = 164), or EPI 30 mg on days 1, 8, and 15 every 28 days for six cycles plus TAM 30 mg/d for 3 years (EPI-TAM, n = 174). In both arms, patients received radiotherapy, delivered after chemotherapy (CT) in the EPI-TAM group. Results The 6-year DFS rates were 69.3% with TAM and 72.6% with EPI-TAM (P = .14). The multivariate analysis shows a relative risk of relapse of 1.93 (95% CI, 1.70 to 2.17) with TAM compared with EPI-TAM (P = .005). The 6-year OS, related to disease progression, was 79.1% and 79.8%, respectively (P = .41). Compliance with CT was good: 96.9% of patients received six cycles. The acute toxicity per patient was mild: grade 2 neutropenia in 5.9%, grade 2 anemia in 2.0%, grade 3 nausea or vomiting in 4.6%, and grade 3 alopecia in 7.2%. Five cases (in five patients) of decreased left ventricular ejection fraction occurred after CT: three after adjuvant CT, and two after anthracycline-based CT for relapse. One patient died as a result of dysrhythmia related to carcinomatous lymphangitis. No secondary leukemia occurred. Conclusion This study conducted in node-positive elderly patients demonstrates a significant contribution of a weekly EPI regimen in terms of DFS. Moreover, this regimen is safe for hematologic, nonhematologic, and cardiac toxicities.

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.

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.

Predictor of trastuzumab-induced cardiotoxicity in breast cancer (BC) patients: HER2/neu 655 polymorphisms, biochemical and clinical features.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1033-1033 ◽  
Author(s):  
Isabel Blancas ◽  
Celia Gómez ◽  
Francisco Javier Martín-Pérez ◽  
Jose Manuel Garrido ◽  
Fernando Rodríguez-Serrano
Keyword(s):  
Breast Cancer ◽  
Clinical Features ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Genotype Frequencies

1033 Background: The introduction of trastuzumab in the treatment scheme of the HER2 BC patients has improved the evolution of the disease. Nevertheless, some of this patients develop cardiotoxicity. We studied some of our population of HER2 positive BC patients treated with trastuzumab trying to find predictors for developing cardiotoxicity, specifically the association of the HER2 Ile655Val A˃G polymorphism with trastuzumab-induced cardiotoxicity and with survival and some biochemical and clinical features. Methods: For the study breast cancer patients were recruited from San Cecilio University Hospital in Granada (Spain) who were treated with trastuzumab. HER2 Ile655Val A˃G polimorphism was performed in 93 patients using Taqman SNP technology. We analyzed the relation of polymorphisms with disease free survival (DFS) and overall survival (OS). We also could asses 66 patients who had biochemical measurement of NTpro BNP during the treatment with trastuzumab and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and body mass index (BMI). Cardiotoxicity was defined as a ≥ 10% decrease of the left ventricular ejection fraction (LVEF) from baseline, a LVEF below 40% or any clinical manifestation of heart insufficiency. NT-proBNP cut-off points were considered to stablish normal or abnormal values adjusted by patient age. Results: Genotype frequencies of HER2/neu 655 met Hardy-Weinberg equilibrium (p = 0.363). Logistic regression analysis adjusted by hormonal status and anthracycline treatment showed higher cardiotoxicity risk for AG vs AA Her2-Ile655 polimorphism (OR = 3.00, CI95% 1.07-8.41, p = 0.037) or for AG vs AA+GG Her2-Ile655 polimorphism (OR = 3.21, CI95% 1.15-8.96, p = 0.026). We did not find association between HER2neu Ile655Val polymorphism and DFS or OS. NT-proBNP baseline higher than the range (OR 5.9, 95% CI 1.2 - 28.5, p = 0.028) and diabetes mellitus (OR 22.0, 95% CI 5.7 - 85.4, p = 0.000) were found to be related with the development of cardiotoxicity. Conclusions: HER2-Ile655 A˃G polymorphism is significantly associated with higher risk of trastuzumab-induced cardiotoxicity but it is not correlated with DFS neither OS. Diabetes or baseline high NT-proBNP levels are predictors for the development of trastuzumab-induced cardiotoxicity. These parameters should be considered for a closer follow up and for preventive actions as accurate glycaemic control for patients who will receive trastuzumab.

Effect of HER2/neu 655 polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1025-1025
Author(s):  
Isabel Blancas ◽  
Celia Martín ◽  
Marta Legerén ◽  
Michel Martos ◽  
Silvia Sequero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Genotype Frequencies

1025 Background: HER2 overexpression in breast cancer is associated with a poor outcome, high risk of metastasis and a reduced overall survival. The introduction of Trastuzumab in the treatment scheme improved the prognosis of these patients. Nevertheless, around 20% of patients develop cardiotoxicity. The purpose of this study is to analyze the association of the HER2 Ile655Val A > G polymorphism with trastuzumab-induced cardiotoxicity and with survival. Methods: The study included 93 patients recruited from San Cecilio University Hospital in Granada (Spain) who were treated intravenously with Trastuzumab. The cardiotoxicity was diagnosed during the treatment follow-up considering a decrease of the left ventricular ejection fraction (LVEF) from baseline or clinical manifestation of congestive heart failure. HER2 655 A > G was genotyping using TaqMan SNP technology. Results: Genotype frequencies of HER2/neu 655 met Hardy-Weinberg equilibrium ( p= 0.363). We did not find differences in baseline LVEF in patients who developed cardiotoxicity vs those who did not. However, in cardiotoxicity group, the symptomatic patients had a baseline LVEF significantly lower than non-symptomatic patients (57.7 vs 66.1, p < 0.028). Logistic regression analysis adjusted by hormonal status and anthracycline treatment showed significant differences between AG and AA (OR = 3.00, CI95% 1.07-8.41, P= 0.037) or AG and AA+GG (OR = 3.21, CI95% 1.15-8.96, P= 0.026). However, we did not find association between Her2/neu Ile655Val polymorphism and disease-free survival or global survival. Conclusions: HER2 655 A > G polymorphism is significantly associated with higher risk of trastuzumab-induced cardiotoxicity but is not associated to a differential survival rate.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Effects ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Neo Adjuvant Chemotherapy

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

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