natriuretic-peptide--brain and Breast-Neoplasms

The natriuretic peptide family (NPs) is a group of natural endocrine hormones, containing a 17-amino acid ring structure connected by disulfide bonds of two cysteines. In this review, the members of the natriuretic peptide family and their corresponding receptors as well as the anti-cancer effects are introduced. Four cardiac hormones of NPs (ANP, VD, KP and LANP) can effectively inhibit the growth of human small cell lung cancer, breast cancer and other tumors and significantly reduce tumor volume in vivo. The in vitro experiments also show that cardiac hormones, CNP and urodilatin can effectively inhibit the growth of most tumor cells. We then further summarized the anti-cancer mechanism of natriuretic peptides. Finally, we introduce several methods that modify natriuretic peptides, leading to enhance their stability and prolong the biological effects of these peptides, which might be helpful for the clinical application in the future. Peptide therapy is a very promising field for cancer treatments since they can induce the death of cancer cells without dramatically affecting normal cells. The synthesis of a useful and stable natriuretic peptide can enhance the effect of cancer treatments and significantly reduce drug resistance and toxicity.

Topics: Breast Neoplasms; Female; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Receptors, Atrial Natriuretic Factor

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.

Topics: Anthracyclines; Biomarkers; Breast Neoplasms; Cardiotoxicity; DNA Topoisomerases, Type II; Early Detection of Cancer; Female; Galectin 3; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peroxidase; Troponin I; Troponin T

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab?

Topics: Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; C-Reactive Protein; Cardiotoxicity; Echocardiography; Echocardiography, Three-Dimensional; Female; Humans; Immunoglobulin E; Incidence; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Receptor, ErbB-2; Trastuzumab; Troponin; Ventricular Dysfunction, Left

To analyze whether BNP could be a potential biomarker for cardiac damage of breast cancer after radiotherapy.. PubMed, Web of Science, ProQuest and Medline were searched using the key words "breast cancer" ("breast tumor", "breast neoplasm", or "breast carcinoma"), "brain natriuretic peptide" (or BNP) and "radiotherapy" (or "radiation therapy"). Four articles were selected and analyzed using the STATA 12.0 software package. The standard mean difference (SMD) and its standard error for BNP were calculated to assess the relationship between BNP and radiotherapy for breast cancer patients.. In total, 172 patients with breast cancer were identified. The pooled SMD was -0.233 (95% CI -1.113, -0.057). The pooled estimated SMD for all studies showed obvious significant difference (z = 3.99, P = .000). There was no publication bias.. This meta-analysis suggested that BNP could be a biomarker of cardiac damage at high heart absorbed doses according to radiotherapy, especially for left breast cancer patients.

Topics: Biomarkers; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Female; Humans; Mastectomy; Natriuretic Peptide, Brain; Radiotherapy, Adjuvant

Although having high clinical efficacy in the treatment of human epidermal growth factor receptor-2 (HER2+) metastatic breast cancer, trastuzumab has been associated with cardiotoxicity, and the etiology and pathogenesis of this condition is currently under investigation.. This paper reviews the cardiotoxicity, associated with trastuzumab use and discusses the risk assessment and management of cardiac dysfunction.. The increased risk of cardiotoxicity is lower when trastuzumab is given as monotherapy (3%-7%) compared with anthracyclines + trastuzumab therapy (27%). Type II cardiac changes occur in trastuzumab-treated patients, which do not appear to be dose-related, are not associated with histological changes, and are generally reversible. Several risk factors for cardiac events have been identified and assessing levels of troponin I and N-terminal pro-brain B-type natriuretic peptide before and after treatment with trastuzumab may allow early detection of cardiotoxicity. A symptomatic and functional evaluation scheme for patients indicated for treatment with trastuzumab has also been proposed to work alongside therapeutic options for the treatment of heart failure.. The risk of cardiac dysfunction associated with trastuzumab can be justified given the increase in overall survival. This risk is lower when trastuzumab is given as monotherapy. The paradigm for cardiologists remains the same: treat the cancer effectively whilst preventing cardiotoxicity.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Receptor, ErbB-2; Risk Factors; Stroke Volume; Trastuzumab; Troponin I

Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies.

Topics: Breast Neoplasms; Cardiotoxicity; Donepezil; Doxorubicin; Female; Humans; Leukocytes, Mononuclear; Metformin; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy.. This study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early-stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1, and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51 ± 8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain deteriorated from baseline in both placebo (+2.0 ± 2.7%, P = 0.002) and perindopril (+0.9 ± 2.5%, P = 0.04), but not with bisoprolol (-0.2 ± 2.1%, P = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3 ± 4.4%, P = 0.004; +130 ± 150%, P ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7 ± 17%, P = 0.02, +8 ± 23%, P = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (-2 ± 10%, P = 0.008, -18 ± 28%, P < 0.001, respectively).. Trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.

Topics: Breast Neoplasms; Cardiotoxicity; Female; Humans; Natriuretic Peptide, Brain; Trastuzumab; Troponin I

Topics: Adult; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cohort Studies; Echocardiography; Female; Germany; Humans; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prevalence; Risk Factors; Stroke Volume; Troponin T

Breast cancer treatment is associated with the occurrence of various cardiac adverse events. One of the mechanisms associated with cardiotoxicity is oxidative stress, against which cells are protected by antioxidative enzymes. Genetic variability of antioxidative enzymes can affect enzyme activity or expression, which modifies the ability of cells to defend themselves against oxidative stress and could consequently contribute to the occurrence of treatment-related cardiotoxicity. Our aim was to evaluate the association of common polymorphisms in antioxidative genes with cardiotoxicity after adjuvant radiotherapy (RT) in HER2-positive breast cancer patients.. Our retrospective study included 101 HER2-positive early breast cancer patients who received trastuzumab and adjuvant RT. We isolated DNA from buccal swabs and used competitive allele-specific PCR for genotyping of. Carriers of at least one polymorphic. In our study, polymorphisms

Topics: Adult; Antineoplastic Agents; Aryldialkylphosphatase; Breast Neoplasms; Cardiotoxicity; Catalase; Female; Glutathione S-Transferase pi; Heart Diseases; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Radiotherapy, Adjuvant; Receptor, ErbB-2; Superoxide Dismutase; Trastuzumab

The antimalarial artesunate (ART), a semisynthetic derivative of artemisinin from the Chinese herb artemisia annua has remarkable anticancer properties in vitro and in vivo. Its excellent safety profile known from short-term therapy in malaria was confirmed in an open phase I trial (ARTIC M33/2) for dose-finding as add-on therapy for four weeks.. Patients with metastatic breast cancer, who had not experienced any clinically relevant adverse events (AE) during participation in ARTIC M33/2, were offered to continue ART as compassionate use (CU). Regular monitoring was continued in order to ensure adequate individual safety and tolerability and to collect information about long-term treatment with ART. Clinically relevant AEs or second progression of disease during ART were reasons for discontinuation of the add-on therapy.. Compassionate use was offered open-label to participants of ARTIC M33/2.. Patients continued to take 100, 150 or 200 mg oral ART daily as add-on therapy to their guideline-based oncological therapy. Clinical and laboratory monitoring included audiological and neurological examination, ECG, NTproBNP and reticulocyte determination. Cumulative treatment days and cumulative ART doses encompass both the phase I study as well as the continued add-on treatment period (CU).. Following the 4 ± 1 weeks of the phase I trial, thirteen patients continued the add-on therapy as CU, resulting in a total of 3825 treatment days. In individual patients up to 1115 cumulative treatment days (37 months) and cumulative ART doses up to 167.3 g were reached. A total of 25 AEs grade ≥ 2 at least possibly related to ART long-term add-on therapy were documented, two, six and 17 in dose groups 100, 150 and 200 mg/d ART respectively. Six of these AEs were classified as grade 3, two in patients taking 150 and four in patients on 200 mg/d, none of them being probably or certainly related to ART.. In thirteen patients with metastatic breast cancer up to 200 mg/d long-term oral ART (2.3-4.1 mg/kg BW/d) in up to 1115 cumulative treatment days (37 months) did not result in any major safety concerns.

Topics: Administration, Oral; Adult; Aged; Artesunate; Breast Neoplasms; Compassionate Use Trials; Creatinine; Female; Humans; Liver; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Treatment Outcome

Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak and cardiac function persisted at 12 months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk.. Women with breast cancer scheduled for AC (n = 28) who participated in a nonrandomized trial of exercise training (ET; n = 14) or usual care (UC; n = 14) during AC completed a follow-up evaluation 12 months post-AC completion (16 months from baseline). At baseline, 4 months, and 16 months, participants underwent a resting echocardiogram (left ventricular ejection fraction; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, and cardiac output (Qc) at rest and during intense exercise.. Seventeen women (UC, n = 8; ET, n = 9) completed evaluation at baseline, 4 months, and 16 months. At 4 months, AC was associated with 18% and 6% reductions in V˙O2peak in the UC and ET groups, respectively, which persisted at 16 months (UC, -16%; ET, -7%) and was not attenuated by ET (interaction, P = 0.10). Exercise Qc was lower at 16 months compared with baseline and 4 months (P < 0.001), which was due to a blunted augmentation of SV during exercise (P = 0.032; a 14% reduction in peak SV), with no changes in heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R = 0.47, P < 0.01).. Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function.. ACTRN12616001602415.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiac Output; Cardiorespiratory Fitness; Cardiotoxicity; Echocardiography; Exercise Therapy; Exercise Tolerance; Female; Heart Rate; Hemoglobins; Humans; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Risk Factors; Stroke Volume; Troponin I

Anthracyclines are chemotherapeutic agents frequently used in breast cancer (BC) treatment. Although it improves disease-free and overall survival, the use of anthracyclines is associated with a cumulative risk of cardiac toxicity. Preventive strategies to optimize cardiac health are needed and exercise is proposed as a potential non-pharmacological approach for counteracting anthracycline-related cardiotoxicity (ARC). Most of the data on the effects of exercise to reduce ACT are from animal studies, with only a few studies in a limited number of patients indicating beneficial effects. To better understand the effectiveness of exercise in the mitigation of ARC, clinical, real-world trials claim require a larger sample size and more accurate and valuable clinical biomarkers. In this study, we intend to include a large sample and investigate cardiac function through serial measures of biomarkers and imaging techniques.. This protocol describes a two-arm, prospective, randomized controlled trial that will explore the cardioprotective effect of a structured exercise program in women with BC undergoing anthracycline-containing chemotherapy (ACT). Ninety adult women with early BC and recommended to receive ACT will be randomly assigned (1:1) to an intervention group or a control group. Patients allocated to the intervention group will perform a supervised exercise program three times per week, consisting of a combination of aerobic and resistance training with progressive intensity and volume, during the time period they receive ACT. The control group will receive standard BC care. Primary outcomes related to cardiac (dys)function will be circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, resting left ventricular (LV) longitudinal strain, and resting LV ejection fraction. Secondary outcomes will include the assessment of resting blood pressure, resting heart rate (HR), resting HR variability (HRV), recovery HR, physical function outcomes, self-reported physical activity level, health-related quality of life, and fatigue. Data will be obtained at baseline (t. The implementation of the present study design, using novel clinical biomarkers, will determine the effect of structured exercise interventions at mitigating ARC, with the overall aim of finding means to further improve BC care.. ISRCTN, ISRCTN32617901 . Registered on 24 October 2018. Last updated on 11 January 2019.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Health Status; Heart Diseases; Hemodynamics; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Portugal; Prospective Studies; Randomized Controlled Trials as Topic; Resistance Training; Risk Factors; Time Factors; Treatment Outcome; Ventricular Function, Left

Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients.. This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel.. 173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2.. These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

Topics: Aged; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cardiovascular Abnormalities; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lapatinib; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Paclitaxel; Receptor, ErbB-2; Trastuzumab; Troponin T

Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response.. Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment.. Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance (p<0.01) decreased, and ejection fraction (p=0.02) and systolic strain rate (p<0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p<0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure.. The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.

Topics: Adult; Blood Pressure; Breast Neoplasms; Cardiac Output; Cardiotoxins; Doxorubicin; Exercise; Exercise Test; Female; High-Intensity Interval Training; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proof of Concept Study; Stroke Volume

Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines.. This report encompasses 121 women included in the 2×2 factorial, placebo-controlled, double-blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240-400 mg/m. Treatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta-blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear.. URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Angiotensin II Type 1 Receptor Blockers; Antibiotics, Antineoplastic; Benzimidazoles; Biomarkers; Biphenyl Compounds; Breast Neoplasms; Cardiotoxicity; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epirubicin; Female; Humans; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Tetrazoles; Treatment Outcome; Troponin I; Troponin T; Ventricular Dysfunction, Left

Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicity during cancer therapy. We report the results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer.. Patients with 0-1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m(2)) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3 months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points.. Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3-38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (±SD) was 19% ± 2% (baseline), 19% ± 2% (month 6), and 19% ± 3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline.. The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer.. Dual anti-HER2 therapy with trastuzumab and pertuzumab in combination with taxane-based chemotherapy improves overall survival in patients with metastatic HER2-positive breast cancer. There is a critical need to investigate the potential cardiotoxicity of dual anti-HER2 blockade, given the importance of HER2 signaling in cardiac homeostasis and stress response. Global longitudinal strain and cardiac biomarkers have been proposed as adjuncts to left ventricular ejection fraction for the early detection of cardiotoxicity. In this phase II study of combination trastuzumab and pertuzumab with paclitaxel, no clinically significant change was observed in global longitudinal strain or cardiac biomarkers. These results further support the cardiac safety of dual anti-HER2 blockade previously reported in the CLEOPATRA study. The findings in the current study also call into question the role of intensive cardiac monitoring among patients treated with anti-HER2 therapy in the absence of anthracyclines. Less frequent cardiac assessments could lead to a reduction in unnecessary treatment interruption and is an important consideration given the rise in medical expenditures, but this requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Cardiotoxicity; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Metastasis; Paclitaxel; Receptor, ErbB-2; Trastuzumab; Troponin I; Ventricular Function, Left

The aim of the present study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to characterize the relationship between plasma doxorubicin and N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations within 48 h of doxorubicin treatment.. The study enrolled 17 female patients with stages 1-3 breast cancer and receiving adjuvant doxorubicin (60 mg m(-2) ) and cyclophosphamide (600 mg m(-2) ) every 14 days for four cycles. In two consecutive cycles, plasma concentrations of doxorubicin, doxorubicinol, troponin and NT-proBNP were collected before infusion, and up to 48 h after the end of doxorubicin infusion. Nonlinear mixed-effects modelling was used to describe the PK-PD relationship of doxorubicin and NT-proBNP.. A three-compartment parent drug with a one-compartment metabolite model best described the PK of doxorubicin and doxorubicinol. Troponin concentrations remained similar to baseline. An indirect PD model with transit compartments best described the relationship of doxorubicin exposure and acute NT-proBNP response. Estimated PD parameters were associated with large between-subject variability (total assay variability 38.8-73.9%). Patient clinical factors, including the use of enalapril, were not observed to be significantly associated with doxorubicin PK or NT-proBNP PD variability.. The relationship between doxorubicin concentration and the acute NT-proBNP response was successfully described with a population PK-PD model. This model will serve as a valuable framework for future studies to identify clinical factors associated with the acute response to doxorubicin. Future studies are warranted to examine the relationship between this acute response and subsequent heart failure. Should such a relationship be established, this model could provide useful information on patients' susceptibility to doxorubicin-induced long-term cardiotoxicity.

Topics: Adult; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Doxorubicin; Female; Humans; Middle Aged; Models, Biological; Natriuretic Peptide, Brain; Peptide Fragments; Troponin

This is the first randomized placebo-controlled evaluation of a medical intervention for the prevention of trastuzumab-related cardiotoxic effects.. To determine as the primary end point whether angiotensin II antagonist treatment with candesartan can prevent or ameliorate trastuzumab-related cardiotoxic effects, defined as a decline in left ventricular ejection fraction (LVEF) of more than 15% or a decrease below the absolute value 45%.. This randomized, placebo-controlled clinical study was conducted between October 2007 and October 2011 in 19 hospitals in the Netherlands, enrolling 210 women with early breast cancer testing positive for human epidermal growth factor receptor 2 (HER2) who were being considered for adjuvant systemic treatment with anthracycline-containing chemotherapy followed by trastuzumab.. A total of 78 weeks of candesartan (32 mg/d) or placebo treatment; study treatment started at the same day as the first trastuzumab administration and continued until 26 weeks after completion of trastuzumab treatment.. The primary outcome was LVEF. Secondary end points included whether the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) can be used as surrogate markers and whether genetic variability in germline ERBB2 (formerly HER2 or HER2/neu) correlates with trastuzumab-related cardiotoxic effects.. A total of 206 participants were evaluable (mean age, 49 years; age range, 25-69 years) 103 in the candesartan group (mean age, 50 years; age range, 25-69 years) and 103 in the placebo group (mean age, 50 years; age range, 30-67 years). Of these, 36 manifested at least 1 of the 2 primary cardiac end points. There were 3.8% more cardiac events in the candesartan group than in the placebo group (95% CI, -7% to 15%; P = .58): 20 events (19%) and 16 events (16%), respectively. The 2-year cumulative incidence of cardiac events was 0.28 (95% CI, 0.13-0.40) in the candesartan group and 0.16 (95% CI, 0.08-0.22) in the placebo group (P = .56). Candesartan did not affect changes in NT-proBNP and hs-TnT values, and these biomarkers were not associated with significant changes in LVEF. The Ala1170Pro homozygous ERBB2 genotype was associated with a lower likelihood of the occurrence of a cardiac event compared with Pro/Pro + Ala/Pro genotypes in multivariate analysis (odds ratio, 0.09; 95% CI, 0.02-0.45; P = .003).. The findings do not support the hypothesis that concomitant use of candesartan protects against a decrease in left ventricular ejection fraction during or shortly after trastuzumab treatment in early breast cancer. The ERBB2 germline Ala1170Pro single nucleotide polymorphism may be used to identify patients who are at increased risk of trastuzumab-related cardiotoxic effects.. clinicaltrials.gov Identifier: NCT00459771.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antineoplastic Agents; Benzimidazoles; Biphenyl Compounds; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Double-Blind Method; Echocardiography; Female; Genetic Variation; Genotype; Humans; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neoplasm Staging; Netherlands; Odds Ratio; Peptide Fragments; Polymorphism, Single Nucleotide; Receptor, ErbB-2; Stroke Volume; Tetrazoles; Trastuzumab; Troponin T; Ventricular Function, Left

Anthracycline-induced cardiotoxicity is (partly) mediated by free radical overload. A randomized study was performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) protects against anthracycline-induced cardiotoxicity as measured by changes in echo, electrocardiography and an array of biomarkers.. Eighty female, chemotherapy-naïve breast cancer patients (median age 49, range 24-67 years) scheduled for four or five courses of adjuvant 3 weekly doxorubicin plus cyclophosphamide (AC) chemotherapy, were randomly assigned to receive 80 mg PC-SOD (human recombinant SOD bound to lecithin) or placebo, administered intravenously (i.v.) immediately prior to each AC course. The primary end point was protection against cardiac damage evaluated using echocardiography, QT assessments and a set of biochemical markers for myocardial function, oxidative stress and inflammation. Assessments were performed before and during each course of chemotherapy, and at 1, 4 and 9 months after completion of the chemotherapy regimen. In all patients cardiac effects such as increases in NT-proBNP concentration and prolongation of the QTc interval were noticed. There were no differences between the PC-SOD and placebo-treated patients in systolic or diastolic cardiac function or for any other of the biomarkers used to assess the cardiac effects of anthracyclines.. PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Cardiotonic Agents; Cardiotoxicity; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Echocardiography; Electrocardiography; Female; Free Radical Scavengers; Humans; Injections, Intravenous; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Phosphatidylcholines; Superoxide Dismutase; Young Adult

To evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.. A total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.. Brain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).. Cardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Bone Marrow; Breast Neoplasms; Cardiovascular Agents; Chemotherapy, Adjuvant; Epirubicin; Female; Follow-Up Studies; Heart Rate; Humans; Leukocyte Count; Middle Aged; Natriuretic Peptide, Brain; Neutrophils; Razoxane; Stroke Volume; Young Adult

For targeting anti-HER-2, trastuzumab-incorporated chemotherapy is the standard for HER-2-overexpressing breast cancer in adjuvant settings. But there are few data on trastuzumab in elderly patients. We evaluated the incidence of adverse events among an elderly population of trastuzumab-treated HER-2-positive breast cancer patients in adjuvant settings.. Data on 39 elderly HER-2 overexpressing breast cancer patients treated with both curative surgery and adjuvant trastuzumab were retrospectively collected from a Japanese multicenter study. The loading dose was 8 mg/kg body weight, and the maintenance dose was 6 mg/kg every 3 weeks; or the loading dose was 4 mg/kg followed by 2 mg/kg weekly as maintenance.. After a median follow-up of 20.0 (2.4-53.9) months, a total of 32 patients (82.1%) completed 1-year trastuzumab treatment. The median treatment duration was 12.0 months (range 2-12; mean 10.5). Adverse events occurred in 11 patients (28.2%). Four (10.2%) discontinued or interrupted treatment after experiencing toxicity. One patient died because of interstitial pneumonia. Three patients (7.7%) had congestive heart failure (CHF), one of whom had a history of angina. Three patients (7.7%) had a lower left ventricular ejection fraction (LVEF), and brain natriuretic peptide elevation was totally observed in three patients (7.7%). Three patients with lower LVEF had received chemotherapy containing doxorubicin before trastuzumab. Of the three patients, two discontinued therapy because of CHF, but all recovered with proper medication containing a diuretic agent.. Elderly patients tolerated trastuzumab well, although careful management is needed.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cohort Studies; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Heart Failure; Humans; Natriuretic Peptide, Brain; Receptor, ErbB-2; Retrospective Studies; Time Factors; Trastuzumab; Treatment Outcome; Ventricular Dysfunction, Left

Anthracyclines are among the most active drugs in breast cancer patients. We planned to evaluate the early and 2-year modification of left ventricular ejection fraction (LVEF) and the effects of chemotherapy on troponin I and neurohormonal assessment.. Patients with early breast cancer surgically treated and eligible to adjuvant chemotherapy were enrolled. All patients underwent clinical assessment, radionuclide ventriculography, troponin I and brain natriuretic peptide (BNP) measurements at baseline and one-month (T1), one year (T2) and 2-year (T3) after chemotherapy. Reductions of LVEF ≥ 10% or an overt heart failure were considered cardiovascular events.. 53 patients, 52 females and 1 male, age 55.3 years were included and followed at T3. A significant reduction of LVEF was observed (from 62 ± 5.5% to 59.3 ± 8.6%, p=0.04) at T3; BNP increased (from 33.4 ± 41.5 pg/ml to 62.7 ± 94.7 pg/ml, p=0.005) at T1. Troponin I augmented at T1 (from 0.006 ± 0.01 ng/ml to 0.05 ± 0.04 ng/ml, p=0.0001) but normalized at T2 (0.005 ± 0.08 ng/ml; p=0.9). Only baseline BNP was nearly to be significantly correlated with T3 LVEF (p=0.07 HR 0.96-1) at multivariate analysis. In 13/53 patients (32.1%) LVEF showed ≥ 10% reduction at T3 (group A); in 40/53 patients (67.9%) LVEF was unchanged (group B). Patients in group A demonstrated higher baseline plasma BNP (p=0.02) and lower haemoglobin concentration (p=0.007) compared to patients in group B.. LVEF and BNP modified early after anthracycline chemotherapy and LVEF did not recover at T3. In patients who developed left ventricular systolic dysfunction, a subclinical activation of neurohormonal profile was observed.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Breast Neoplasms, Male; Combined Modality Therapy; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Troponin I; Ventricular Dysfunction, Left

rhuMAb 2C4 (pertuzumab, RO4368451), a human epidermal growth factor receptor-2 (HER2) targeted antibody that binds to an epitope distinct from trastuzumab, blocks ligand-associated heterodimerization of HER2 with other HER receptor family members. This study evaluated the toxicity, pharmacokinetics and anti-tumor activities of pertuzumab in Japanese patients with solid tumors.. Patients with solid tumors refractory to standard therapy were administered pertuzumab 5, 10, 15, 20 and 25 mg/kg intravenously once every 3 weeks. Grade 3 toxicities were considered as dose limiting. The maximum tolerated dose (MTD) was a dose at which two out of six patients had Grade 3 toxicities.. Eighteen patients, aged 38-66 (median 57) years, with solid tumors were enrolled and a total of 32 cycles of pertuzumab were administered. Toxicities were generally acceptable. Grade 3 elevation of gamma-glutamyl transpeptidase was observed in one patient at 25 mg/kg and was considered to be dose limiting. MTD was not reached up to a dose level of 25 mg/kg. The serum concentration of pertuzumab declined slowly (terminal half-life is approximately 3 weeks). The AUC proportionally increased over the dose range tested. There was limited evidence of activity (stable disease 2; progressive disease 13; and not evaluable 3); however, tumor shrinkage and tumor marker decrease were observed in an ovarian cancer and a non-small-cell lung cancer patient, respectively.. Pertuzumab is well tolerated up to 25 mg/kg. Although objective tumor response was not observed, it is worth evaluating as a flat dose and in combination with other cytotoxics and molecular-targeted agents.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Area Under Curve; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Diarrhea; Digestive System Neoplasms; Drug Eruptions; Female; Humans; Hypersensitivity; Lung Neoplasms; Lymphopenia; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms, Unknown Primary; Ovarian Neoplasms; Radiotherapy, Adjuvant; Receptor, ErbB-2

Cardiac function impairment is a known side effect of epirubicin-based chemotherapy. Activation of natriuretic peptides is demonstrated in patients with heart failure.. To identify prospectively the cardiotoxic profile of epirubicin-based chemotherapy in breast cancer patients and to evaluate the sensitivity of proANP and NT-proBNP as early biochemical markers of cardiac dysfunction.. Forty cancer patients divided in two nonrandomized groups received either epirubicin and paclitaxel (Group A, n=26) or mitoxantrone and docetaxel (Group B, n=14). Control groups, Group C (n=13) and Group D (n=20), consisted of female patients with heart failure and healthy women respectively. Natriuretic peptides and LVEF were determined in all patients.. A statistically significant difference was recorded regarding LVEF before and after treatment in Group A patients (p=0.0001). Three patients had a significant LVEF decline between 10% and 18% from baseline values, while three reached an LVEF value below 50%. All of them presented an increase in proANP and NT-proBNP values (mean increase 270.31+/-124 fmol/ml and 303.57+/-108 fmol/ml, respectively). A significant correlation between the increase in plasma proANP (r=0.8, p<0.0001), as well as NT-proBNP (r=0.7, p<0.0001) and the decrease in LVEF was observed. Regarding Group A, levels of proANP increased from 192.25 fmol/ml before treatment to 287.84 fmol/ml after treatment (p=0.0001), whereas NT-proBNP increased from 152.50 to 242 fmol/ml (p<0.0001) respectively. During follow up, two Group A patients developed congestive heart failure twelve and fourteen months after the completion of chemotherapy respectively. A significant LVEF decline was recorded in both patients during the episode. Regarding Group B, no statistically significant differences were demonstrated.. ProANP and NT-proBNP levels might be used as reliable and sensitive markers in the detection of early cardiac impairment caused by epirubicin-based chemotherapy.

Topics: Adult; Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Breast Neoplasms; Cardiovascular Diseases; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Protein Precursors

Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A.. 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed.. Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59-35.3).. Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity; Female; Humans; Incidence; Natriuretic Peptide, Brain; Prospective Studies

Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited.. To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard.. In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study.. Sequential therapy with anthracyclines and trastuzumab.. Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models.. Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD.. Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually.. ClinicalTrials.gov Identifier: NCT02306538.

Topics: Adult; Breast Neoplasms; Echocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Stroke Volume; Trastuzumab; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Anthracyclines; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Female; Humans; Natriuretic Peptide, Brain; Stroke Volume

The present exploratory study investigated the diagnostic value of inflammatory markers in patients with breast cancer to predict anti-tumour treatment-related cardiac events.. Twenty-one patients with breast cancer were enrolled in this prospective observational study and followed over 6 months. Transthoracic echocardiography and measurement of cardiac (N-terminal prohormone of brain natriuretic peptide (NT-proBNP), troponin I (TnI)) and inflammatory biomarkers (vascular adhesion molecule 1 (VCAM-1), soluble suppression of tumorigenesis-2 (sST2), adiponectin) was performed at 3-month intervals (baseline, follow-up, final visit). Cardiac events were defined as decrease in left ventricular ejection fraction (LVEF, decrease by 10% or <50%) or increase in global longitudinal strain (GLS, increase by 15% or > -16%), as a more sensitive marker of LV function.. Cardiac deterioration was observed in 9 out of 21 patients (event group). While LVEF did not differ significantly between the two groups (event vs. no event) at any visit, GLS was significantly higher during follow-up (follow-up: event -16 ± 3.3% vs. no event -18 ± 1.6%, p = 0.04; final visit: event -16 ± 2.1% vs. no event -19 ± 1.9%, p = 0.003). NT-proBNP was numerically higher in patients with a cardiac event during all visits, with NT-proBNP negatively correlated with LVEF and MAPSE (both r = -0.33, p = 0.02), whereas GLS (r = 0.40, p = 0.006), TnI (r = 0.44, p = 0.001), and VCAM-1 (r = 0.48, p = 0.003) showed a positive association with NT-proBNP. In comparison, higher VCAM-1 and sST2 concentrations were detected in the event group at both baseline and the final visit, with a significant difference for baseline (VCAM-1: p = 0.02; sST2: p = 0.03). Adiponectin was also lower in patients with a treatment-related event. Thresholds for VCAM-1 >762 ng/mL and sST2 >18.7 ng/mL, as detected by ROC analysis, correlated best with the primary endpoint.. Cardiac events during anti-tumour treatment in patients with breast cancer are relatively common. Inflammatory markers such as VCAM-1 or sST2 were associated with an increased likelihood for occurrence of a treatment-related event, which may therefore hold the promise to better identify patients at high risk.

Topics: Adiponectin; Biomarkers; Breast Neoplasms; Female; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prognosis; Stroke Volume; Troponin I; Vascular Cell Adhesion Molecule-1; Ventricular Function, Left

Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data.. Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2).. Higher IL-10 levels were observed in the case group compared to controls at T1 (. Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

Topics: Biomarkers; Breast Neoplasms; Cardiotoxicity; Doxorubicin; Female; Follow-Up Studies; Humans; Interleukin-10; Natriuretic Peptide, Brain; Peptide Fragments

Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage.. This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage.. The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Topics: Breast Neoplasms; Cardiotoxicity; Clinical Protocols; Echocardiography; Endothelial Cells; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Radiation Dosage; Radiation Injuries; Stroke Volume; Troponin T; Ventricular Dysfunction, Left

To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer.. We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated.. There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279).. Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Topics: Aged; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity; Female; Humans; Intraoperative Care; Mastectomy, Segmental; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiotherapy, Adjuvant; Troponin I

Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed.. Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures.. Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping,. Normal myocardium (%) derived by fast-strain-encoded cardiovascular magnetic resonance, is an accurate and sensitive tool that can establish cardiac safety in patients with cancer undergoing cardiotoxic chemotherapy not only for the early detection but also for the prediction of those at risk of developing CTX. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03543228.

Topics: Aged; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Early Diagnosis; Female; Follow-Up Studies; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Time Factors; Troponin I; Ventricular Function, Left

The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)-measured native T. Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability.. A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T. The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.

Topics: Adult; Anthracyclines; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Case-Control Studies; Female; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Time Factors; Trastuzumab; Troponin I

We measured peak oxygen consumption (VO

Topics: Aged; Biomarkers; Breast Neoplasms; Cancer Survivors; Cardiorespiratory Fitness; Cohort Studies; Female; Heart; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Radiation Injuries; Radiotherapy Dosage

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value <50%. Associations between changes in biomarkers and left ventricular ejection fraction were evaluated in repeated-measures linear regression models. Cox regression models assessed the associations between biomarkers and CTRCD. Early increases in all biomarkers occurred with anthracycline-based regimens. hs-cTnT levels >14 ng/L at anthracycline completion were associated with a 2-fold increased CTRCD risk (hazard ratio, 2.01; 95% CI, 1.00-4.06). There was a modest association between changes in NT-proBNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI, -1.8 to -0.4] with each NT-proBNP doubling). Increases in NT-proBNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI, 1.32-1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI, 1.04-1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01173341.

Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Growth Differentiation Factor 15; Heart Disease Risk Factors; Heart Diseases; Humans; Longitudinal Studies; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Placenta Growth Factor; Predictive Value of Tests; Prospective Studies; Risk Assessment; Time Factors; Trastuzumab; Troponin T

Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.. We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age.. 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2-28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7-85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity.. NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Pharmacological; Breast Neoplasms; Cardiotoxicity; Diabetes Mellitus; Drug Monitoring; Female; Heart Disease Risk Factors; Heart Failure; Humans; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Receptor, ErbB-2; Retrospective Studies; Stroke Volume; Trastuzumab; Ventricular Function, Left

The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC).. Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results.. A 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%.. TRC 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.. Low 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).

Topics: Adult; Anthracyclines; Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cohort Studies; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Receptor, ErbB-2; Stroke Volume; Trastuzumab; Troponin T

GDF-15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF-15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF-15 to other cardiac biomarkers and the general association of GDF-15 on prognosis in an unselected cohort of treatment-naïve cancer patients.. We prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF-15 concentrations were determined alongside other cardiac and routine laboratory markers. All-cause mortality was defined as primary endpoint.. GDF-15 levels were 338 ng/L (IQR:205-534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF-15 [435 ng/L (IQR:279-614) vs 266 ng/L (IQR:175-427), P < .001]. GDF-15 correlated positively with inflammatory status reflected by CRP, SAA and IL-6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NT-proBNP, hsTnT, MR-proADM and CT-proET-1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF-15 was significantly associated with all-cause mortality after multivariate adjustment [adj.HR for ln(GDF-15) 1.78, 95%CI:1.47-2.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF-15 with outcome in myelodysplastic and myeloproliferative disease.. Elevated plasma GDF-15 is associated with progressing disease severity and poor prognosis in solid tumours of treatment-naïve cancer patients. GDF-15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF-15 represents a promising target for our pathophysiologic understanding in cardio-oncology linking conditions of both cardiac and neoplastic disease.

Topics: Adrenomedullin; Aged; Breast Neoplasms; C-Reactive Protein; Cause of Death; Endothelin-1; Female; Gastrointestinal Neoplasms; Glycopeptides; Growth Differentiation Factor 15; Humans; Interleukin-6; Lung Neoplasms; Male; Middle Aged; Mortality; Myelodysplastic Syndromes; Myeloproliferative Disorders; Natriuretic Peptide, Brain; Neoplasm Metastasis; Neoplasms; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Serum Amyloid A Protein; Troponin T

Left-sided breast cancer patients treated with radiotherapy (RT) are at risk for late radiation-induced cardiovascular complications.. The aim of this study was to investigate the BNP plasma levels in long-term breast cancer survivors who received only RT as well to assess whether cardiac dose was associated with BNP values.. Plasma samples for BNP measurement were repeated in 29 patients (63 ± 11 years) who were alive at 5 years after radiotherapy, free of heart disease and available to provide new blood sample. All patients had BNP measurements at baseline. The ΔBNP was measured to analyze the role of marker variations. No patients received chemotherapy.. At 5 years after radiotherapy, median plasma BNP levels remained within the normal range, but the delta-BNP levels are directly related to the heart and ventricular dose received.

Topics: Aged; Breast Neoplasms; Cancer Survivors; Female; Humans; Middle Aged; Natriuretic Peptide, Brain

To evaluate the prognostic potential of lipopolysaccharide-binding protein (LBP) levels after breast cancer radiation therapy (RT) for incipient cardiac dysfunction.. In this single-centered study, we prospectively enrolled female patients treated for left breast cancer. Healthy age- and sex-matched participants were recruited as controls. LBP levels, cardiac troponin T, N-terminal propeptide of the brain natriuretic peptide, fatty acid binding protein, and C-reactive protein were assessed at three timepoints-before RT, after the last RT fraction, and 1 month after the last fraction. Echocardiographic evaluation was done 3 to 3.75 years after RT.. We recruited 51 patients and 78 controls. Baseline LBP concentrations in the study group were significantly higher than in controls at baseline (P < .001), at 24 hours, and at 1 month after RT (P = .003 and P < .001, respectively). Other biomarkers (cardiac troponin T, N-terminal propeptide of the brain natriuretic peptide, fatty acid binding protein, and C-reactive protein) did not differ in any of the timepoints. Posttreatment LBP concentrations were significantly and positively correlated with heart- and lung-associated dose-volume histogram variables. Posttreatment and follow-up LBP levels correlated positively with the E/E' echocardiographic index reflective of the diastolic function. After adjustment for left anterior descending artery mean dose, left ventricle mean dose, mean heart dose, and type of surgery, LBP remained significantly correlated with E/E' when measured 24 hours after RT (beta = 0.41, P = .032) and 1 month after RT (beta = 0.43, P = .028).. Serum LBP concentrations correlate with diastolic function evaluated 3 years after the completion of RT, making LBP a potentially useful prognostic parameter.

Topics: Acute-Phase Proteins; Biomarkers; Breast Neoplasms; C-Reactive Protein; Carrier Proteins; Case-Control Studies; Echocardiography; Fatty Acid-Binding Proteins; Female; Heart; Humans; Lung; Membrane Glycoproteins; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiation Injuries; Time Factors; Troponin T

Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership.. Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class.. Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain.. Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long-term risk of heart failure, particularly in those with modest LVEF declines.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Echocardiography; Female; Heart Failure; Humans; Incidence; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Troponin T; Ventricular Dysfunction, Left

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

Topics: Adult; Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; Cardiac-Gated Imaging Techniques; Cardiotoxicity; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Reproducibility of Results; Risk Factors; Sodium Pertechnetate Tc 99m; Stroke Volume; Time Factors; Tomography, Emission-Computed; Trastuzumab; Treatment Outcome; Troponin I; Ventricular Dysfunction, Left; Ventricular Function, Left

Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF).. In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured.. Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information.. Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF.

Topics: Adult; Aged; Anthracyclines; Biomarkers, Pharmacological; Biomarkers, Tumor; Breast Neoplasms; Female; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; MicroRNAs; Middle Aged; Natriuretic Peptide, Brain; Neoplastic Cells, Circulating; Peptide Fragments; Troponin T

Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are molecular markers that may allow earlier detection of drug-induced cardiotoxicity. In this analysis we aimed to quantify the kinetics and exposure-response relationships of LVEF, troponin T and NT-proBNP measurements, in patients receiving anthracycline and trastuzumab. Repeated measurements of LVEF, troponin T and NT-proBNP and dosing records of anthracyclines and trastuzumab were available from a previously published clinical trial. This trial included 206 evaluable patients with early breast cancer. Exposure to anthracycline and trastuzumab was simulated based on available dosing records and by using a kinetic-pharmacodynamic (K-PD) and a fixed pharmacokinetic (PK) model from literature, respectively. The change from baseline troponin T was described with a direct effect model, affected by simulated anthracycline concentrations, representing myocyte damage. The relationship between trastuzumab and LVEF was described by an indirect effect compartment model. The EC

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Breast Neoplasms; Cardiotoxicity; Female; Heart Ventricles; Humans; Middle Aged; Muscle Cells; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab; Troponin T

Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation.. Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured.. Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values.. In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cations; Cyclophosphamide; Doxorubicin; Electrocardiography; Female; Follow-Up Studies; Heart Conduction System; Heart Diseases; Humans; Middle Aged; Natriuretic Peptide, Brain; Paclitaxel; Prospective Studies; Troponin I

The current study was to evaluate soluble ST-2 level and left ventricular ejection fraction (LVEF) in patients with breast cancer receiving doxorubicin or trastuzumab treatment for 6 months and determine whether soluble ST-2 level can be used to predictive left ventricular function impairment.Patients who were diagnosed as having breast cancer receiving doxorubicin or trastuzumab or combined therapy were enrolled. Demographic data, prior medical history and related medical therapy, and site and stage of breast cancer information were collected from electronic health record. Fasting blood was used to detect soluble ST-2 and brain natriuretic peptide (BNP) levels before and after 6 months doxorubicin or trastuzumab therapy. Echocardiography was performed before and after 6 months of doxorubicin or trastuzumab therapy.Participants were divided into 3 groups based on tertiary soluble ST-2 level. Compared with 1st tertiary group, patients in the 3rd tertiary group had higher proportion receiving combined therapy (14.3% vs 4.7%, P < .05). Baseline soluble ST-2 level was similar across groups. After 6 months' therapy, soluble ST-2 level was significantly higher in the 3rd tertiary group. Pearson correlation analysis showed that soluble ST-2 level was positively correlated with left ventricular volume and E/e' ratio while negatively correlated with LVEF. Doxorubicin, trastuzumab, combined therapy, soluble ST-2 level, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment were all independently associated with LVEF change.In breast cancer patients receiving doxorubicin or trastuzumab therapy, soluble ST-2 level can be used to predict cardiac function and structure changes.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Doxorubicin; Echocardiography; Female; Heart Ventricles; Humans; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke Volume; Trastuzumab; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathy, Dilated; Doxorubicin; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Liver Neoplasms; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Trastuzumab following anthracycline causes cardiotoxicity in up to 28% of patients. Although the cardiotoxicity is often irreversible once cardiac dysfunction is detected, the early predictor has not been established yet.. We prospectively observed breast cancer patients treated with anthracycline or trastuzumab at Tonan Hospital. All patients underwent echocardiography and blood sampling at baseline, and every three months during chemotherapy. Cardiotoxicity was defined as a decline in left ventricular ejection fraction >10% points.. Of 40 patients, 34 patients (85%) were treated with anthracycline (epirubicin), 18 (45%) with trastuzumab, and 12 (30%) with both agents. Cardiotoxicity was observed in four patients (10%), who were all treated with both agents. The absolute levels of high-sensitive troponin T (hs-TnT) were increased in all four patients with cardiotoxicity, and all the highest points were observed before or at the time of detection of cardiotoxicity. The highest level of hs-TnT was not significantly different in patients with and without cardiotoxicity. "Hs-TnT increment from baseline to the highest value" and "hs-TnT integration value above baseline" were significantly greater in patients with cardiotoxicity (0.039 vs. 0.007 ng/mL, P = 0.046, 0.113 vs. 0.022 ng months/mL, P = 0.013, respectively). The integration value had 100% sensitivity and specificity with a cutoff level at 0.070 ng months/mL.. Hs-TnT assay may be able to predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients, and the hs-TnT increment or hs-TnT integration value above baseline was more reliable than the absolute value.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Echocardiography; Epirubicin; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Trastuzumab; Troponin T

Chemotherapy and radiotherapy for breast cancer may lead to cardiac dysfunction, but the prevalence of long-term echocardiographic evidence of cardiac dysfunction is unknown among survivors.. In a cross-sectional study in primary care, we included 350 women who survived breast cancer for at least 5 years after diagnosis (treated with chemotherapy and/or radiotherapy) and 350 matched women (age and primary care physician). The primary outcome was cardiac dysfunction, defined as a left ventricular ejection fraction (LVEF) < 54% and an age-corrected decreased left ventricular (LV) diastolic function. Secondary outcomes included serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, newly diagnosed cardiovascular diseases and cardiovascular medication.. The median age at diagnosis was 63 (interquartile range (IQR) 57-68) years for the breast cancer survivors. Median follow-up after diagnosis was 10 (IQR 7-14) years. LVEF < 54% was present in 52 (15.3%) survivors and 24 (7%) controls (OR 2.4, 95%CI 1.4-4.0), but there was no significant increased prevalence of either LVEF < 50% or LV diastolic dysfunction. Serum NT-proBNP levels were increased, cardiovascular disease was more frequently diagnosed and cardiovascular medication use was more frequent among survivors compared with controls. These associations remained after adjustment for relevant covariates at diagnosis and at follow-up.. In the long term, breast cancer survivors are at increased risk of mild LV systolic dysfunction, increased NT-proBNP levels, and cardiovascular disease compared with matched controls, even after adjustment for cardiovascular risk factors. Previous breast cancer treatment with chemotherapy, radiotherapy or both should be considered when assessing a patient's cardiovascular risk profile.

Topics: Adult; Aged; Breast Neoplasms; Cardiovascular Diseases; Cross-Sectional Studies; Echocardiography; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Doxorubicin (DOX) and trastuzumab (TRA) are associated with cardiac dysfunction.. High-sensitivity troponin T (hs-TnT) and brain natriuretic peptide attached to the amino acid N-terminal fragment in the prohormone (NT-proBNP) were measured before and on days +1, +2, +3, and +7 during cycles 1 and 2 of therapy with DOX or TRA in breast cancer patients.. Five of eleven DOX-treated women, compared with 2/11 TRA-treated women, had undetectable baseline hs-TnT. By day +1 of cycle 2, all the DOX-treated women (p = 0.03) but only 7/11 TRA-treated women (p = ns) had detectible hs-TnT. Time to peak was 1-2 days for both groups. In the DOX-treated women, hs-TnT showed significant peaks from precycle baseline, increases in precycle 1 to precycle 2 levels, and a cycle 1 to cycle 2 peak and area under the curve (AUC). hs-TnT increased from precycle (1, 4.6 ± 6.3 pg/mL) to a cycle 2 peak of 16.1 ± 15.0 pg/mL (p < 0.002). No increases were seen with the TRA treatment. Transient posttreatment increases in NT-proBNP were seen after both therapies.. DOX was associated with increased pretreatment baseline, peak, and AUC hs-TnT levels. Both DOX and TRA acutely perturb NT-proBNP. Assessment of pre- and posttreatment hs-TnT could be a means of quantifying cumulative myocardial injury in the course of chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Area Under Curve; Breast Neoplasms; Doxorubicin; Female; Humans; Immunoassay; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; ROC Curve; Trastuzumab; Troponin T

Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study. Patients with missing marker assessments were excluded, resulting in 452 evaluable patients. A primary cardiac end point was defined as symptomatic congestive heart failure of New York Heart Association class III or IV, confirmed by a cardiologist, and a significant LVEF drop, or death of definite or probable cardiac causes. A secondary cardiac end point was defined as a confirmed significant asymptomatic or mildly symptomatic LVEF drop. Results Elevated baseline troponin I (> 40 ng/L) and T (> 14 ng/L), occurring in 56 of 412 (13.6%) and 101 of 407 (24.8%) patients, respectively, were associated with an increased significant LVEF drop risk (univariate analysis: hazard ratio, 4.52; P < .001 and hazard ratio, 3.57; P < .001, respectively). Few patients had their first elevated troponin value recorded during the study (six patients for troponin I and 25 patients for troponin T). Two patients developed a primary and 31 patients a secondary cardiac end point (recovery rate of 74%, 23 of 31). For NT-proBNP, higher increases from baseline were seen in patients with significant LVEF drop. Conclusion Elevated troponin I or T before trastuzumab is associated with increased risk for TRCD. A similar conclusion for NT-proBNP could not be drawn because of the lack of a well-established elevation threshold; however, higher increases from baseline were seen in patients with TRCD compared with patients without.

Topics: Adult; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; Proportional Hazards Models; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Stroke Volume; Trastuzumab; Troponin I; Troponin T

Topics: Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Humans; Immunoglobulin E; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab; Troponin I; Troponin T

Anti-neoplastic chemotherapy can determine various side effects, including cardiotoxicity, and no real guidelines for its early detection and management have been developed. The aim of this study is to find some plasmatic markers able to identify breast cancer patients that are at greater risk of developing cardiovascular complications during chemotherapy, in particular heart failure. A prospective study on 100 breast cancer patients with mean age of 66 years in adjuvant treatment with anthracyclines, taxanes, and trastuzumab was performed. Patients underwent cardiological examination before starting treatment (T0) and at 3 months (T1), 6 months (T2), and 1 year (T3) after treatment. Evaluation of serum cardiac markers and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed at T0, T1, T2, and T3, simultaneously to electrocardiogram and echocardiogram, showing a significant increase in NT-proBNP concentration (p > 0.0001) at T1, T2, and T3, before left ventricular ejection fraction decrease became evident. Human epidermal growth factor receptor 2 (HER2)-negative patients were more susceptible to mild hematological cardiotoxicity, while HER2-positive patients were more susceptible to severe cardiotoxicity. A significant correlation between NT-proBNP increased values after chemotherapy and prediction of mortality at 1 year was evidenced. From our experience, serum biomarker detection was able to support an early diagnosis of cardiac damage, also in the absence of left ventricular ejection fraction decrease. Therefore, the evaluation of specific plasmatic markers for cardiac damage is more sensitive than echocardiography in the early diagnosis of chemotherapy-related cardiotoxicity; furthermore, it can also add a prognostic value on outcome.

Topics: Aged; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Creatine Kinase, MB Form; Electrocardiography; Female; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Receptor, ErbB-2; Troponin T; Ventricular Function, Left

The early detection of anthracycline- induced cardiotoxicity is very important since it might be useful in prevention of cardiac decompensation. This study was designed with the intent of assessing the usefulness of cardiac troponin T (cTnT) and NT- Pro BNP estimation in early prediction of anthracycline induced cardiotoxicity.. In this prospective study histologically proven breast cancer patients who were scheduled to receive anthracycline containing combination chemotherapy as a part of multimodality treatment were enrolled. Baseline cardiac evaluation was performed by echocardiography (ECHO) and biomarkers like cardiac troponin T (cTnT) and N terminal- pro brain natriuretic peptide (NT- Pro BNP). All patients underwent cTnT and NT- Pro BNP estimation within 24 hours of each cycle of chemotherapy and were followed up after 6 months of initiation of chemotherapy. Any changes in follow up ECHO were compared to ECHO at baseline and cTnT and NT- Pro BNP levels after each cycle of anthracycline-based chemotherapy.. Initial data were obtained for 33 patients. Mean change in left ventricular diastolic diameter (LVDD) within 6 months was 0.154± 0 .433 cms (p value=0.049). Seven out of 33 patients had an increase in biomarker cTnT levels (p value=0.5). A significant change in baseline and follow up LVDD was observed in patients with raised cTnT levels (p value=0.026) whereas no change was seen in ejection fraction (EF) and left atrial diameters (LAD) within 6 months of chemotherapy. NT- Pro BNP levels increased in significant number of patients (p value ≤0.0001) but no statistically significant change was observed in the ECHO parameters within 6 months.. Functional monitoring is a poorly effective method in early estimation of anthracycline induced cardiac dysfunction. Estimation of biomarkers after chemotherapy may allow stratification of patients in various risk groups, thereby opening window for interventional strategies in order to prevent permanent damage to the myocardium.

Topics: Adult; Aged; Anthracyclines; Biomarkers; Breast Neoplasms; Cardiotoxins; Early Diagnosis; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; Prognosis; Prospective Studies; Troponin T; Ventricular Dysfunction, Left

Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended.. The aim of our study was to prospectively assess baseline patients' characteristics, level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic parameters as possible predictors of trastuzumab-related cardiac dysfunction.. In a prospective cohort study, clinical, echocardiographic and neurohumoral assessment was performed at baseline, after 4, 8 and 12 months in breast cancer patients undergoing post-anthracycline (3-4 cycles) adjuvant therapy with trastuzumab. Trastuzumab-related cardiac dysfunction was defined as a decline of ≥ 10% in left ventricular ejection fraction (LVEF).. 92 patients (mean age, 53.6 ± 9.0 years) were included. Patients who developed trastuzumab-related LVEF decline ≥ 10% (20.6%) during treatment had significantly higher baseline LVEF (70.7 ± 4.4%) than those without (64.8 ± 5.5%) (p = 0.0035). All other measured baseline parameters (age, body mass index, arterial hypertension, level of NT-proBNP and other echocardiographic parameters) were not identified as significant.. Our findings suggest that baseline patient' characteristics, level of NT-proBNP and echocardiographic parameters, as long as they are within normal range, are not a reliable tool to predict early trastuzumab-related cardiac dysfunction in patients undergoing post-low dose anthracycline adjuvant trastuzumab therapy. A LVEF decline in patients with high-normal baseline level although statistically significant is not clinically relevant.

Topics: Adult; Aged; Animals; Anthracyclines; Antineoplastic Agents; Blood Pressure; Body Mass Index; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Echocardiography, Doppler; Female; Heart Failure; Humans; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Receptor, ErbB-2; Reference Values; Risk Factors; Stroke Volume; Time Factors; Trastuzumab; Treatment Outcome

Topics: Aged; Aged, 80 and over; Biomarkers; Breast Neoplasms; Female; Galectin 3; Heart Injuries; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Radiation Injuries; Troponin I

The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP) in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF). Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23), a group that received chemotherapy + tamoxifen (n=21), and a group that received only tamoxifen (n=16). Plasma levels of NT-proBNP were assessed at 0 (T0), 6 (T6), and 12 (T12) months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Topics: Adult; Analysis of Variance; Antineoplastic Agents, Hormonal; Biomarkers; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Echocardiography; Female; Fluorouracil; Follow-Up Studies; Humans; Middle Aged; Natriuretic Peptide, Brain; Paclitaxel; Peptide Fragments; Statistics as Topic; Stroke Volume; Tamoxifen

Trastuzumab induced cardiotoxicity (TIC) was defined as the most serious side effect. Long term cardiac effects of trastuzumab are still not known, thus we aimed to compare the long term cardiac effects of adjuvant trastuzumab therapies of HER2-positive breast cancer according to the treatment duration.. Patients who completed adjuvant trastuzumab treatment at least 6 months before for the adjuvant setting in HER2-positive breast cancer were included in the study. A total of 164 patients were included in this study: 108 and 56 patients were treated with 9 weeks and 52 weeks of trastuzumab, respectively. The main limitation of our study is that due to the cross-sectional evaluation of cardiac biomarkers we cannot predict the status of baseline cardiac biomarkers of this population.. The median follow-up of the study was 32 (10-95) months. The accompanying chronic diseases were similar in both groups. Baseline left ventricular ejection fraction (LVEF) was 65.5 ± 3.4% vs 67.1 ± 4.5% in the 9 weeks and 52 weeks trastuzumab treatment groups, respectively (p = 0.13). Symptomatic heart failure was not observed during trastuzumab treatment in either group. Trastuzumab induced cardiotoxicity (TIC) was observed in 2 (1.9%) and 17 (30.3%) patients in the 9 and 52 weeks trastuzumab treatment groups, respectively (p < 0.001). After a median 24 months of follow-up from the last dose of trastuzumab, mean LVEF values were similar between the two treatment arms (p = 0.29). In the subgroup analyses, mean LVEF values were significantly lower in patients who developed TIC compared to those who did not develop TIC (61.9 ± 3.6% vs 64.4 ± 2.6%, p = 0.04). Average mean LVEF loss from baseline was significantly higher in patients who developed TIC compared to those who did not develop TIC (10.0 ± 6.0% vs 1.5 ± 6.2%, p < 0.001). Cardiac biomarkers were similar in both treatment groups. In the subgroup analyses serum High-sensitivity C-reactive protein (hs-CRP) and prohormone brain natriuretic peptide (pro-BNP) levels were significantly higher in patients who developed TIC compared to those who did not develop TIC.. TIC was observed to be significantly higher in the 52 weeks trastuzumab group. At the end of 32 months of follow-up mean LVEF values and cardiac biomarkers were similar between the two treatment groups. In the subgroup analyses, significant LVEF loss and higher cardiac biomarkers which show cardiac damage in patients who developed TIC can be permanent in some of the patients and long term cardiac damage may be underestimated.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; C-Reactive Protein; Cardiotoxicity; Cross-Sectional Studies; Early Detection of Cancer; Early Medical Intervention; Female; Heart; Heart Diseases; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptor, ErbB-2; Stroke Volume; Time; Trastuzumab

Adjuvant trastuzumab with chemotherapy is the treatment of choice for patients with human epidermal growth factor receptor positive (HER2+) breast cancer and improves the outcome of patients with early breast cancer. However, it is potentially cardiotoxic and there are no validated methods of early detection of cardiotoxicity from trastuzumab following anthracycline-based chemotherapy. Currently, changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Early identification of patients at risk for cardiotoxic effects is a primary goal for both cardiologists and oncologists. Plasma markers such as b-type natriuretic peptide (BNP - an index of elevated filling pressure) and troponin I (TnI - an index of cardiomyocyte damage) may be used to identify the risk of developing cardiac dysfunction during treatment. In this review, we discuss if TnI and/or BNP could be used to help the prevention or treatment of cardiac dysfunction at the earliest possible time.

Topics: Adjuvants, Immunologic; Anthracyclines; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Early Detection of Cancer; Female; Humans; Natriuretic Peptide, Brain; Risk Assessment; Trastuzumab; Troponin I

Identification of patient with increased risk of cardiotoxicity would allow not only prevention and early diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy.. Fifty-two women with HER2(+) breast cancer treated with trastuzumab were included in this study. Patients were prospectively followed with routine cardiac evaluation. Before and after administration of trastuzumab blood samples for NT-proBNP were also taken.. The median age was 48.5 year (range: 26-74). Hypertension and obesity were two most common co-morbidities. The median duration application of trastuzumab was 52 weeks. During median 14.5 (3-33) months follow-up cardiac adverse events occurred in 5 (9.6%) patients and 2 out of 5 was grade III-IV heart failure. Both patients had preserved left ventricular ejection fraction and no symptom of heart failure before trastuzumab but older than 65 years old and had diabetes mellitus and obesity. High level of NT-proBNP (> 300 ng/ml) was observed in both patients and heart failure recovery was not observed. There was statistically significant difference regarding body mass index (p = 0.004) and diabetes mellitus (p = 0.002) between patients with and without cardiotoxicity.. Although, cardiac biomarkers still cannot replace routine cardiac monitoring, natriuretic peptides may provide additional tool for detection of patients with high risk of cardiotoxicity and early detection of cardiotoxicity.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Biomarkers; Breast; Breast Neoplasms; Cardiotoxicity; Female; Follow-Up Studies; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab

Assessing a diverse biomarker panel (NT-proBNP, TNF-α, galectin-3, IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after treatment with anthracyclines.. Of 55 breast cancer patients biomarkers were assessed and echocardiography was performed one year after treatment with anthracyclines.. 29.1% of patients showed abnormal biomarker levels: NT-proBNP in 18.2%, TNF-α and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt-1 were normal in all patients. A correlation between left ventricular ejection fraction (LVEF) and NT-proBNP was observed (r = -0.564, p ≤ 0.01).. The evaluated biomarkers do not contribute to early detection. Future research should focus on NT-proBNP.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cardiovascular Diseases; Cyclophosphamide; Docetaxel; Doxorubicin; Echocardiography; Electroencephalography; Enzyme-Linked Immunosorbent Assay; Female; Galectin 3; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Taxoids; Tumor Necrosis Factor-alpha; Young Adult

Adjuvant radiotherapy (RT) for left-sided breast cancer increases cardiac morbidity and mortality. For the heart, no safe radiation threshold has been established. Troponin T is a sensitive marker of myocardial damage. Our aim was to evaluate the effect of left-sided breast cancer RT on serum high sensitivity troponin T (hscTnT) levels and its association with cardiac radiation doses and echocardiographic parameters.. A total of 58 patients with an early stage, left-sided breast cancer or ductal carcinoma in situ (DCIS) who received adjuvant breast RT without prior chemotherapy were included in this prospective, non-randomized study. Serum samples were taken before, during and after RT. An increase of hscTnT >30 % was predefined as significant. A comprehensive 2D echocardiograph and electrocardiogram (ECG) were performed before and after RT. Dose-volume histograms (DVHs) were generated for different cardiac structures.. The hscTnT increased during RT from baseline in 12/58 patients (21 %). Patients with increased hscTnT values (group A, N = 12) had significantly higher radiation doses for the whole heart (p = 0.02) and left ventricle (p = 0.03) than patients without hscTnT increase (group B, N = 46). For the left anterior descending artery (LAD), differences between groups A and B were found in volumes receiving 15 Gy (p = 0.03) and 20 Gy (p = 0.03) Furthermore, after RT, the interventricular septum thickened (p = 0.01), and the deceleration time was prolonged (p = 0.008) more in group A than in group B.. The increase in hscTnT level during adjuvant RT was positively associated with the cardiac radiation doses for the whole heart and LV in chemotherapy-naive breast cancer patients. Whether these acute subclinical changes increase the risk of excessive long-term cardiovascular morbidity or mortality, will be addressed in the follow-up of our patients.

Topics: Aged; Biomarkers; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Echocardiography, Doppler; Electrocardiography; Female; Heart; Humans; Mastectomy; Mastectomy, Segmental; Middle Aged; Natriuretic Peptide, Brain; Organs at Risk; Prospective Studies; Radiation Injuries; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Radiotherapy, Image-Guided; Sensitivity and Specificity; Troponin T

Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity.. In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered.. Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78 (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions.. Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.

Topics: Adult; Antineoplastic Agents; Biomarkers; Breast; Breast Neoplasms; C-Reactive Protein; Cardiotoxicity; Cardiotoxins; Doxorubicin; Female; Galectin 3; Growth Differentiation Factor 15; Heart; Humans; Longitudinal Studies; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Trastuzumab; Troponin I; Vascular Endothelial Growth Factor Receptor-1

Anthracycline chemotherapy remains an integral part of the care for curative intent chemotherapy in breast cancer and non-Hodgkin lymphoma patients. Better tools need to be identified to predict cardiac complications of anthracycline chemotherapy.. We investigated the utility of high-sensitivity cardiac troponin T (hscTnT), N-terminal pro-B-type natriuretic peptide, cardiac troponin T and I, and creatine kinase (CK)-MB in cancer patients receiving anthracycline-based chemotherapy, in order to determine whether baseline levels or changes in these biomarkers may help predict the onset of congestive heart failure.. Eighteen consecutive patients with a pathologic diagnosis of breast cancer or non-Hodgkin lymphoma were enrolled. The median dose of doxorubicin exposure was 240 mg/m(2) (range 240-400 mg/m(2)). After treatment with doxorubicin, the hscTnT increased to 19.1 pg/mL (P<0.001). CKMB and N-terminal pro-B-type natriuretic peptide levels increased to 1.1 ng/mL and 88.3 pg/mL, respectively (P=0.02). When subjects who had a decline in left ventricular ejection fraction (LVEF) by equilibrium radionuclide ventriculography were compared to those who did not have a change in LVEF, there was a suggestion that those subjects with an elevated baseline hscTnT were more likely to have a decline in LVEF (2.7 pg/mL and 0.1 pg/mL, respectively; P=0.07). Spearman correlation demonstrated that patients with higher baseline hscTnT and CKMB tended to have a greater decline in LVEF (Spearman correlation -0.54, 95% confidence interval -0.80 to -0.08 [P=0.02], and -0.49, 95% confidence interval -0.77 to -0.01 [P=0.04], respectively).. Elevations in baseline hscTnT levels are suggestive of an oncology subgroup at high risk of developing cardiac complications from their chemotherapy. Early detection by oncologists with the use of baseline biomarkers may be clinically important in designing interventions to prevent serious anthracycline-based chemotherapy complications.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Creatine Kinase, MB Form; Doxorubicin; Early Diagnosis; Female; Heart Diseases; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Risk Factors; Stroke Volume; Treatment Outcome; Troponin I; Troponin T; Up-Regulation; Ventricular Function, Left

Accurate detection and monitoring of disease-related biomarkers is important in understanding pathophysiology. We devised a rapid immunoreaction system that uses submicrometer polymer-coated fluorescent ferrite (FF) beads containing both ferrites (magnetic iron oxide) and fluorescent europium complexes.. FF beads were prepared by encapsulation of hydrophobic europium complexes into the polymer layers of affinity magnetic beads using organic solvent. A sandwich immunoassay using magnetic collection of antibody-coated FF beads to a specific place was performed. Brain natriuretic peptide and prostate-specific antigen were selected as target detection antigens to demonstrate the feasibility of this approach. An immunohistochemical staining using magnetic collection of antibody-coated FF beads onto carcinoma cell samples was also performed.. The sandwich immunoassays, taking advantage of the magnetic collection of antibody-coated FF beads, detected target antigens within 5 min of sample addition. Without magnetic collection, the sandwich immunoassay using antibody-coated FF beads required long times, similar to conventional immunoassays. Using the magnetic collection of antibody-coated FF beads, immunohistochemical staining enabled discrimination of carcinoma cells within 20 min.. This proof of principle system demonstrates that immunoreactions involving the magnetic collection of antibody-coated FF beads allow acceleration of the antigen-antibody reaction. The simple magnetic collection of antibody-coated FF beads to a specific space enables rapid detection of disease-related biomarkers and identification of carcinoma cells.

Topics: Biomarkers; Breast Neoplasms; Carcinoma, Squamous Cell; Cell Line, Tumor; Coordination Complexes; ErbB Receptors; Esophageal Neoplasms; Europium; Female; Ferric Compounds; Fluorescent Dyes; Humans; Immunoassay; Lung Neoplasms; Magnets; Male; Natriuretic Peptide, Brain; Prostate-Specific Antigen; Small Cell Lung Carcinoma

The goal of this study was to determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury.. Cancer survivors who receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or if these doses are associated with changes in quality of life (QOL).. In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity, late gadolinium enhancement, serum B-type natriuretic peptide, troponin I, and the impact of treatment on QOL before and 1, 3, and 6 months after receipt of Anth-bC.. Participants averaged 50 ± 2 (range 19 to 80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m(2) of doxorubicin-equivalent chemotherapy. Left ventricular end-systolic volume (48 ± 3 ml to 54 ± 3 ml; p = 0.02), left ventricular strain (-17.7 ± 0.4 to -15.1 ± 0.4; p = 0.0003), pulse wave velocity (6.7 ± 0.5 m/s to 10.1 ± 1 m/s; p = 0.0006), and QOL deterioration (15.4 ± 3.3 to 28.5 ± 3.9; p = 0.008) increased, whereas LVEF (58 ± 1% to 53 ± 1%; p = 0.0002) decreased within 6 months after low to moderate doses of Anth-bC. All findings persisted after accounting for age, gender, race (white/black), doxorubicin-equivalent dose, doxorubicin administration technique, comorbidities associated with CV events, and cancer diagnosis (p = 0.02 to 0.0001 for all). There were no new late gadolinium enhancement findings after 6 months.. In these study patients, low to moderate doses of Anth-bC were associated with the early development of subclinical abnormalities of cardiac and vascular function that in other populations are associated with the future occurrence of CV events.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiovascular Diseases; Female; Humans; Leukemia; Lymphoma; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulse Wave Analysis; Quality of Life; Risk Factors; Stroke Volume; Surveys and Questionnaires; Time Factors; Troponin I; Vascular Stiffness; Ventricular Function, Left; Young Adult

The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established.. Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle.. A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported.. Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Receptor, ErbB-2; Safety; Trastuzumab; Ventricular Function, Left

Cardiac dysfunction is a major limitation of anthracycline treatment in cancer patients. There are several useful serum markers in other types of cardiomyopathy, including N-terminal pro-brain-natriuretic peptide (NT-proBNP), troponin-T and creatine kinase MB isoform. We investigated the potential application of these serum biomarkers in cancer patients receiving treatment with anthracycline.. We collected data from 52 female breast cancer patients receiving doxorubicin and cyclophosphamide every 3 weeks for four cycles. Cardiac function evaluations by echocardiography were done at baseline and at the end of the fourth cycle of chemotherapy. Patients' blood samples were serially measured for cardiac biomarkers.. The mean cumulative dose of doxorubicin in this study was 237 mg/m(2) . No symptomatic heart failure was detected during the study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from mean ± SD 70.7 ± 6% at baseline to 67.0 ± 5% (P < 0.001). By clinical toxicity criteria the LVEF decline was grade I in 18% and grade II in 4%. After one dose of chemotherapy, a significant rise of serum NT-proBNP occurred in patients who subsequently developed an LVEF reduction compared with patients with normal LVEF (P = 0.04). A correlation analysis demonstrated that the reduction of fractional shortening was significantly associated with elevated NT-proBNP (r = -0.016, P = 0.014).. Asymptomatic reductions in cardiac function are common in breast cancer patients treated with doxorubicin. NT-proBNP may serve as a convenient serum biomarker for the early detection of cardiotoxicity induced by anthracycline.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Early Diagnosis; Echocardiography; Female; Follow-Up Studies; Heart Diseases; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; Prognosis; Prospective Studies

Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B–type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer.. NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography.. NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7–333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0–172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V(3 Gy)(%) (p = 0.001), the ratios (p = 0.01), the ratios D(15 cm)(3)/D(50%) (Gy) (p = 0.008) for the heart and correlations between plasma levels and V(2 Gy) (%) (p = 0.002), the ratios (p = 0.03), and the ratios (p = 0.05) for the ventricle.. Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non–RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small percentage of organ volumes (heart or ventricle) receiving high dose levels, supporting the notion that the heart behaves as a serial organ.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Biomarkers; Breast Neoplasms; Case-Control Studies; Echocardiography; Female; Heart; Heart Ventricles; Humans; Middle Aged; Natriuretic Peptide, Brain; Organs at Risk; Peptide Fragments; Radiation Dosage; Radiation Injuries; Tomography, X-Ray Computed; Troponin I

We present the case of a 42-year-old Japanese woman who developed acute heart failure after chemotherapy with epirubicin for breast cancer. Echocardiography revealed a cardiac dysfunction with left ventricular thrombus. Serial serum troponin T tests were positive over a 5-week period, and an endomyocardial biopsy demonstrated ultrastructural lesions which were similar to those caused by cardiotoxicities due to doxorubicin. Although the patient developed splenic thromboembolism, her cardiac function recovered gradually, and she regained full range of her activities. This case report demonstrates that epirubicin-associated cardiotoxicity causes life-threatening heart failure and supportive care is important until the patient recovers from acute intoxication.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Epirubicin; Female; Fibrin Fibrinogen Degradation Products; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Spleen; Thromboembolism; Troponin T

Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab.. Eighty-one women with newly diagnosed human epidermal growth factor receptor 2-positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro-B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%-43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%-14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure.. In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.

Topics: Adult; Anthracyclines; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Chi-Square Distribution; Echocardiography; Female; Heart Diseases; Humans; Interleukin-1 Receptor-Like 1 Protein; Logistic Models; Middle Aged; Multivariate Analysis; Myocardial Contraction; Natriuretic Peptide, Brain; North America; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Receptors, Cell Surface; Risk Assessment; Risk Factors; Stroke Volume; Taxoids; Time Factors; Trastuzumab; Troponin I; Ventricular Function, Left

Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.. The study-population was a historical cohort comprising 980 women who were randomized to receive one of two adjuvant regimens for treatment for BC: 7-9 cycles of cyclophosphamide-epirubicin-5-fluorouracil [CEF (600 + 60 + 600 mg/m(2))] or cyclophosphamide-methotrexate-5- fluorouracil [CMF (600 + 40 + 600 mg/m(2))]. We collected information in national registries of death and diagnoses and a sample of 77 survivors was examined with tissue-Doppler imaging (TDI), echocardiography, radionuclide ventriculography and N-terminal-pro-B-type-natriuretic peptide (NT-proBNP), an established marker for heart failure.. Median follow-up was 12 years (39 days-20 years). Fifty-one percent had died. Incidence of CHF was 2.6/1000/year and equal in the treatment groups. In the sample, individuals who had received CEF showed no cardiac impairment when compared to individuals who received CMF. NT-proBNP-levels were within normal limits but higher in the CEF-group than in the CMF-group (confidence limits 105-226%, p = 0.03). Results of our study seem reassuring regarding the long-term risk of cardiotoxicity following low-dose adjuvant epirubicin treatment. However, larger, longitudinal studies are needed to establish the clinical implications.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Chemotherapy, Adjuvant; Cohort Studies; Cyclophosphamide; Denmark; Drug Administration Schedule; Echocardiography; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Heart; Heart Failure; Humans; Methotrexate; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Radionuclide Ventriculography; Registries; Stroke Volume; Time Factors

As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro-B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro-B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardiotoxicity and its associated morbidity and mortality.

Topics: Adult; Anthracyclines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Echocardiography; Female; Humans; Natriuretic Peptide, Brain; Stroke Volume; Trastuzumab; Treatment Outcome; Troponin C; Ventricular Dysfunction, Left

The aim of this study was to evaluate whether cardiac biomarkers, tissue velocity (TVI) and strain imaging, and cardiac magnetic resonance imaging can predict early left ventricular (LV) dysfunction in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting.. Early indexes of LV systolic dysfunction with noninvasive cardiac imaging would be useful for addressing the cardiac safety profile of trastuzumab, potentially avoiding the detrimental effects of heart failure.. We used cardiac biomarkers, TVI and strain imaging, and cardiac magnetic resonance imaging to detect pre-clinical changes in LV systolic function, before conventional changes in left ventricular ejection fraction (LVEF) in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting.. Of 42 patients (mean age 47 ± 9 years) prospectively followed between 2007 and 2009, 10 (25%) developed trastuzumab-mediated cardiomyopathy (CM). Troponin T, C-reactive protein, and brain natriuretic peptide did not change over time. Within 3 months of adjuvant therapy with trastuzumab, there was a significant difference in the lateral S' between the normal cohort and the CM group (9.1 ± 1.6 cm/s and 6.4 ± 0.6 cm/s, respectively, p < 0.05). Similarly, the peak global longitudinal and radial strain decreased as early as 3 months in the trastuzumab-mediated cardiotoxicity group. As compared with both global longitudinal and radial strain, only S' was able to identify all 10 patients who developed trastuzumab-mediated CM. The LVEF subsequently decreased at 6 months of follow-up in all 10 patients, necessitating discontinuation of the drug. All 10 patients demonstrated delayed enhancement of the lateral wall of the LV within the mid-myocardial portion, consistent with trastuzumab-induced CM.. Both TVI and strain imaging were able to detect pre-clinical changes in LV systolic function, before conventional changes in LVEF, in patients receiving trastuzumab in the adjuvant setting.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Breast Neoplasms; C-Reactive Protein; Echocardiography, Doppler; Female; Heart; Humans; Magnetic Resonance Imaging, Cine; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptor, ErbB-2; Risk Assessment; Sensitivity and Specificity; Trastuzumab; Troponin T; Ventricular Dysfunction, Left

Although systolic and diastolic left ventricular functions after cancer chemotherapy are well studied, there are a few investigations about the right ventricular functions. We aimed to investigate the early effects of chemotherapy on right heart, if any, in addition to the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and right heart echocardiographic indices.. Thirty-seven consecutive patients with newly diagnosed breast cancer who were planned to receive either AC protocol [cyclophosphamide (600 mg/m(2)) + adriamycin (60 mg/m(2))] or CAF protocol [cyclophosphamide (600 mg/m(2)) + adriamycin (60 mg/m(2)) + 5-fluorouracil (600 mg/m(2))] for six cures were enrolled between February 2009 and June 2010. Echocardiography was performed before the onset of the chemotheurapeutic regimen (T1), on the day after the completion of the first cure (T2), and after the completion of two cures of the regimen (T3). Serum NT-proBNP levels were also measured at T1, T2, and T3. The mean right ventricular fractional area change (RVFAC) was 63.7 ± 3.63, 63.3 ± 3.67, and 61.2 ± 4.41% at T1, T2, and T3, respectively (pT1-T3 and pT2-T3 <0.05). Tricuspid annular plane systolic excursion (TAPSE) has decreased in time (1.82 ± 0.2, 1.78 ± 0.19, and 1.62 ± 0.24 cm; pT1-T2, pT1-T3, and pT2-T3 were 0.002, <0.001, and <0.001, respectively). Tricuspid annular mean E'/A' ratios were 1.42 ± 0.16, 1.36 ± 0.18, and 1.11 ± 0.32 (pT1-T2 = 0.013, pT1-T3 < 0.001, and pT2-T3 < 0.001). Mean tricuspid annular systolic velocities were 11.35 ± 1.85, 11.0 ± 1.82, and 10.45 ± 1.75 cm/s for T1, T2, and T3; and the differences between T1 and T2, T1 and T3, and T2 and T3 were all significant (P = 0.005, <0.001, and 0.001). Median serum NT-proBNP levels were 82 (60-247), 116 (60-426), and 170 (60-600) pg/mL at T1, T2, and T3. The amount of change in RVFAC and TAPSE between T1 and T3 were found to be correlated with the amount of change in NT-proBNP measurements between T1 and T3 (R: -0.7, P < 0.001; R: -0.62, P < 0.001).. There is a subclinical decrease in right ventricular systolic and diastolic echocardiographic indices, although mostly, in the normal range, in a relatively short time interval after onset of chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Echocardiography, Doppler; Female; Fluorouracil; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Right

As there is no method to detect trastuzumab-related cardiotoxicity (TRC) preclinically, patients are monitored with serial assessments of left ventricular ejection fraction (LVEF) with instigation of cardiac therapy and possible interruption of trastuzumab therapy if TRC develops. Serum cardiac biomarkers, including troponins and natriuretic peptides, represent possible tools to detect cardiotoxicity at a preclinical level.. We sought biochemical evidence of cardiac damage or strain in a cohort of women already receiving trastuzumab by performing a cross-sectional study of serum cardiac biomarkers. All patients had a normal LVEF and no clinical evidence of cardiac failure. Serum troponin I and N-terminal pro-B type natriuretic peptide (NT pro-BNP) were assayed immediately prior to trastuzumab infusion (t0; n = 36) and 24 hours later (t24; n = 31).. Troponin I was not elevated in any patient at t0 or t24. Overall 14/36 (39%) patients had at least one NT pro-BNP level above the upper limit of normal (ULN) and both levels were above the ULN in 8/31 (26%) patients. There was no significant change in NT pro-BNP from t0 to t24.. NT pro-BNP levels are elevated in a significant proportion of patients with normal LVEF receiving trastuzumab. Troponin I levels are not raised in this group, perhaps reflecting the mechanism of cardiotoxicity. The data provide biochemical evidence of subclinical cardiac strain in women receiving trastuzumab. Results are exploratory and have informed the design of a larger study examining the predictive utility of serial serum NT pro-BNP levels for TRC in the adjuvant setting.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cohort Studies; Cross-Sectional Studies; Female; Heart Function Tests; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab; Troponin I

The aim of this study was to assess the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting late cardiotoxicity in patients treated with not-high-dose chemotherapy (NHDC), and to compare the predictive value of NT-proBNP and cardiac troponin I (cTnI).. In 71 patients undergoing NHDC with anthracyclines, NT-proBNP and cTnI levels were measured before and 24 h after each NHDC cycle. Left ventricular (LV) function was assessed by echocardiography at baseline, every two NHDC cycles, at the end of chemotherapy, and at 3-, 6- and 12-month follow-up.. During NHDC, only NT-proBNP showed abnormal values. According to NT-proBNP behaviour, patients were divided into two groups: group A (n=50) with normal (n=23) or transiently elevated NT-proBNP levels (n=27), and group B (n=21) with persistently elevated NT-proBNP levels. At follow-up, LV impairment was significantly worse in group B than in group A. %Δ (baseline-peak) NT-proBNP was predictive of LV impairment at 3-, 6- and 12-month follow-up, with a cutoff of 36%.. Serial measurements of NT-proBNP may be a useful tool for the early detection of patients treated with NHDC at high risk of developing cardiotoxicity.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Cardiovascular Diseases; Cyclophosphamide; Docetaxel; Doxorubicin; Echocardiography; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Taxoids; Troponin I; Ventricular Function, Left

Radiation therapy to the mediastinum and breast can be associated with cardiac complications. Cardiac damage may manifest early during radiation therapy or occur late, years after radiation therapy has been finished.. Myocardial damage is associated with the release of both troponin I (TnI) and brain natriuretic peptide (BNP). The current study sought to determine whether radiation treatment to the mediastinum and breast leads to the release of cardiac biomarkers.. The study comprised 23 patients: 18 with lung cancer and 5 with breast cancer. Radiation therapy was performed for up to 6 weeks. Total radiation dose was >45 Gy in each patient with a dose of 1.8 Gy per fraction. Blood samples to determine TnI and BNP were taken before and once a week during radiation therapy. Echocardiography was done before and after radiation had been finished.. Two patients died during the study. Both TnI and BNP levels increased significantly during the study (log(10) scale); however, absolute and mean values remained on a relatively low level (mean preradiation and postradiation TnI: 0.007 +/- 0.008, 0.014 +/- 0.01 ng/ml; mean preradiation and postradiation BNP: 123 +/- 147, 159 +/- 184 pg/ml).. Radiation therapy leads to cardiac cell damage and changes in the left ventricular loading conditions as suggested by a significant increase of the cardiac biomarkers TnI and BNP. Determination of serum levels seems to be superior to echocardiography in detecting radiation-induced cardiac damage. Serial measurements of cardiac biomarkers may facilitate the management of patients undergoing radiation therapy and may help to define subgroups at high risk of developing heart failure.

Topics: Aged; Biomarkers; Breast Neoplasms; Echocardiography; Female; Heart; Heart Failure; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Radiation Dosage; Radiation Injuries; Troponin I

Anthracyclines are well established and highly efficacious antineoplastic agents for various haematopoietic and solid tumours, such as breast cancer. The main adverse effect of anthracycline therapy is cardiotoxicity. The aim of this prospective study was to determine the role of plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in assessing left ventricular function in early breast cancer patients receiving adjuvant anthracycline treatment.. Thirty-three newly diagnosed breast cancer patients who received a total doxorubicin dosage of 240 mg/m2 over four treatment cycles as part of adjuvant chemotherapy after curative breast surgery were included in this study. Venous NT-proBNP levels were measured before and at the end of doxorubicin therapy. Left ventricular function was measured by echocardiography conducted 3 weeks after surgery and at the end of doxorubicin therapy.. NT-proBNP levels were significantly higher in patients (n=10) with decreased left ventricular ejection fraction (LVEF) [p=0.02]. There was no difference in LVEF (p=0.164) or NT-proBNP levels (p=0.844) between the patients who had high NT-proBNP levels and those who had normal NT-proBNP levels before doxorubicin chemotherapy. None of the factors studied (breast cancer grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, age) was found to be significantly related to NT-proBNP.. The association between higher NT-proBNP levels and reduced LVEF in asymptomatic breast cancer patients after doxorubicin administration could be an early indication of subclinical acute anthracycline cardiotoxicity. Furthermore, breast cancer patients experiencing a progressive increase in NT-proBNP levels might be in a higher risk group for acute anthracycline cardiotoxicity.

Topics: Adult; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiovascular Diseases; Chemotherapy, Adjuvant; Doxorubicin; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ventricular Function, Left

Chemotherapy with epirubicin is approved in women with breast cancer and is associated with a certain degree of cardiotoxicity.. Epirubicin changes stroke volume, cardiac output and systemic vascular resistance, while liposomal doxorubicin does not.. 75 patients with HER-2-positive metastatic breast cancer were continuously measured with CW-Doppler ultrasound for stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) before, during and after drug infusion in combination with NT-pro-BNP before and 10 min after drug infusion.. Epirubicin infusion increased stroke volume significantly in low-level NT-pro-BNP (62+/-23 ml vs. 74+/-29 ml, p=0.004) and high-level NT-pro-BNP (48+/-5 ml vs. 64+/-20 ml, p=0.131), while liposomal doxorubicin infusion increased stroke volume significantly in low-level NT-pro-BNP (54+/-16 ml vs. 67+/-22 ml, p=0.001) and high-level NT-pro-BNP (65+/-22 ml vs. 82+/-27 ml, p=0.001). Cardiac output was significantly increased in epirubicin (p=0.004) by 20% (NT-pro-BNP<125 pg/ml) and not significantly 38% (NT-pro-BNP>125 pg/ml; p=0.144), while in liposomal doxorubicin cardiac output was significantly increased by 23% (NT-pro-BNP<125 pg/ml; p=0.023) and 33% (NT-pro-BNP>125 pg/ml; p=0.001). In liposomal doxorubicin cardiac index was significantly increased by 26% (NT-pro-BNP<125 pg/ml; p=0.021) and 33% (NT-pro-BNP>125 pg/ml; p=0.0001). SVR was significantly reduced during and after epirubicin therapy.. Using the CW-Doppler USCOM a different hemodynamic response to epirubicin vs. liposomal doxorubicin is evident. Epirubicin leads to a significant upregulation of stroke volume and cardiac output, which is even more pronounced in the high-level NT-pro-BNP group, while liposomal doxorubicin does not change immediate hemodynamics. No deterioration of cardiac function using the real-time CW-Doppler ultrasound USCOM or an increase in NT-pro-BNP levels was evident during epirubicin or liposomal doxorubicin therapy.

Topics: Adult; Aged; Breast Neoplasms; Cardiac Output; Doxorubicin; Drug Monitoring; Epirubicin; Female; Humans; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography, Doppler

Circulating apoptotic proteins are increased in patients with heart failure. We evaluated whether circulating soluble (s) apoptosis-related proteins and inflammation markers are increased in long-term disease free breast cancer survivors and associated with cardiotoxicity, and if subgroups could be identified based on the applied treatments. Circulating tumour necrosis factor (TNF) alpha, sTNF-receptor (sTNF-R) 1 and 2, sFas, sFas ligand, sTNF-related apoptosis inducing ligand (sTRAIL) and serum HER2 were measured with immunoassay. High-sensitivity C-reactive protein (HS-CRP), fibrinogen, plasma B-type and N-terminal atrial natriuretic peptide (NT-ANP and BNP) were also determined. Thirty-four patients with median 6.0 years follow-up and 12 healthy age-matched women were enrolled. Chemotherapy, consisting of five cycles fluorouracil, epirubicin (90 mg/m(2)), cyclophosphamide (FEC) (n=14) or four cycles FEC followed by myeloablation with high-dose carboplatin, cyclophosphamide, thiotepa (n=20), preceded irradiation and tamoxifen. Circulating apoptosis markers were higher in patients than in controls. No associations with cardiac dysfunction were observed. sFas ligand and sTRAIL were higher in the high-dose than in the standard-dose group. In conclusion, we observed increased circulating apoptotic protein levels in long-term disease-free breast cancer survivors, treated with adjuvant chemoradiotherapy, particularly after myeloablative chemotherapy. The potential relation with late cardiotoxicity of antineoplastic therapy deserves further study.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Atrial Natriuretic Factor; Breast Neoplasms; C-Reactive Protein; Cross-Sectional Studies; Disease-Free Survival; fas Receptor; Female; Heart Failure; Humans; Membrane Glycoproteins; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Radiotherapy; Receptor, ErbB-2; Tamoxifen; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha

The cardiac and antineoplastic effects of trastuzumab may be related to specific uptake of trastuzumab in myocardium and tumor tissue, respectively. We evaluated whether indium-111 (111In)-labeled trastuzumab scintigraphy can predict cardiotoxicity and identify tumor lesions. In addition, we evaluated whether plasma markers for cardiac dysfunction can be used to predict cardiotoxicity.. Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer underwent gamma camera imaging from 15 minutes to 7 days after injection of 150 MBq 111In-diethylenetriamine penta-acetic acid anhydride (DTPA) -trastuzumab, after loading-dose trastuzumab, and after once-a-week trastuzumab doses for 11 weeks, and concomitant paclitaxel once every 3 weeks. Cardiac assessments were performed before treatment, and after four and six cycles. Plasma N-terminal probrain natriuretic peptide (NT-proBNP) and serum troponin I were measured with immunoassay.. Fifteen of the 17 patients were available for cardiac and tumor uptake analysis. On the first scan, myocardial 111In-DTPA-trastuzumab uptake was observed in one patient with pre-existing cardiac arrhythmias, who did not develop heart failure during treatment. Severe cardiotoxicity occurred in three patients, without initial myocardial uptake, whereas one showed weak myocardial uptake after four cycles. The detection rate of single tumor lesions was 45%. New tumor lesions were discovered in 13 of 15 patients. Pretreatment plasma NT-proBNP levels were higher in patients with than without heart failure (mean, 534 [standard deviation, 236] v 105 [standard deviation, 79] ng/L; P = .009).. Radiolabeled trastuzumab scintigraphy was not valuable in predicting trastuzumab-related cardiotoxicity in metastatic breast cancer patients, but can identify HER2-positive tumors. Measurement of plasma NT-proBNP is promising regarding prediction of trastuzumab-related cardiotoxicity.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Disease Progression; Female; Heart Diseases; Heart Neoplasms; Humans; Indium Radioisotopes; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Metastasis; Paclitaxel; Pentetic Acid; Peptide Fragments; Predictive Value of Tests; Receptor, ErbB-2; Tomography, Emission-Computed, Single-Photon; Trastuzumab; Troponin I

A family of six hormones, i.e. atrial natriuretic peptide, brain natriuretic peptide, C-natriuretic peptide, long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide's main known biologic properties are sodium and water excreting and blood pressure lowering.. These six hormones, each at their 1-microm concentrations, were evaluated for their ability to decrease the number and/or proliferation of breast adenocarcinoma cells in culture for 24, 48, 72, and 96 h.. Within 24 h, vessel dilator, long-acting natriuretic peptide, kaliuretic peptide, atrial natriuretic peptide and 8-bromo-cyclic GMP, a cell-permeable analogue of their intracellular mediator cyclic GMP (each at 1 microm), decreased the number of breast adenocarcinoma cells 60%, 31%, 27%, 40%, and 31%, respectively. There was no proliferation in the 3 days following this decrease in breast adenocarcinoma cell number. These same hormones decreased DNA synthesis 69% to 85% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of breast adenocarcinoma cells or inhibit their DNA synthesis. Vessel dilator, long-acting natriuretic peptide, kaliuretic peptide and 8-bromo-cyclic GMP (each at 1 microM) decreased the number of cells in the S phase of the cell cycle by 62%, 33%, 50%, and 39%, respectively (all P < 0.05). Natriuretic peptide receptors-A and -C were present in the breast adenocarcinoma cells.. Four peptide hormones significantly decrease the number of human breast adenocarcinoma cells within 24 h and inhibit the proliferation of these cells for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis and a decrease in cells in the S phase of the cell cycle mediated in part by cyclic GMP.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Blotting, Western; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; DNA; Female; Guanylate Cyclase; Hormones; Humans; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptide Fragments; Protein Precursors; Receptors, Atrial Natriuretic Factor

Topics: Aromatase Inhibitors; Arthroscopy; Atrial Natriuretic Factor; Breast Neoplasms; Estrogen Replacement Therapy; Exercise; Food Labeling; Health Care Costs; Heart Failure; Homocysteine; Humans; Knee Joint; Mosquito Control; Natriuretic Peptide, Brain; Peer Review, Research; Stents

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Epirubicin; Female; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Radionuclide Ventriculography; Ultrasonography; Ventricular Dysfunction, Left