Abstract P3-15-11: Chemotherapy-related fatigue in low cardiac risk breast cancer patients: A sign of cardiotoxicity?

Abstract BACKGROUND: Fatigue in breast cancer patients receiving chemotherapy is a common occurrence and is related to multiple factors. Limited studies exist regarding fatigue as an early symptom of cardiotoxicity. HYPOTHESIS: Fatigue will occur in a majority of early stage breast cancer patients receiving adjuvant chemotherapy despite normal systolic function by echocardiogram and cardiac magnetic resonance imaging (CMR). METHODS: We prospectively enrolled 20 patients with stage I-IIb breast cancer undergoing adjuvant anthracycline or trastuzumab based chemotherapy. Mean age 49 ± 12 years. Seventeen patients completed all 4 time points. CMR, echocardiography and cardiac biomarkers were obtained at 4 different time-points: baseline, during chemotherapy and then 2 weeks and 6 months after completion of chemotherapy. A heart failure questionnaire was completed at each time point with physical examination. Statistics were analyzed by a linear mixed model. RESULTS: Symptoms of fatigue increased during chemotherapy but did not reach statistical significance (table 1). CMR detected significant increases in LV end-diastolic and end-systolic volumes and a significant decrease LV ejection fraction (table2). Biomarkers of cardiac injury troponin I, c-reactive protein, and brain natriuretic peptide did not change significantly. CONCLUSION: Transient fatigue occurred in a majority of patients during chemotherapy but was not clinically significant. However, transient increases in volumetric size did reach statistical significance and paralleled fatigue symptoms. These changes may indicate early cardiotoxicity. SYMPTOM AND CLINICAL RESPONSE TO CHEMOTHERAPYVariableBaselineAfter 2nd Cycle of Chemotherapy2 Weeks After Last Cycle of Chemotherapy6 Months After Last Cycle of ChemotherapyP ValueSYMPTOMATOLOGY     Fatigue (%)0.0047.3421.0510.530.112Chest Pain (%)5.265.265.265.261.000Palpitations (%)10.5310.535.265.260.392Dyspnea (%)0.0010.5310.530.000.801Edema (%)0.000.005.260.000.392PND (%)0.005.260.000.000.392CLINICAL     SBP (mmHg)118.50 ± 11.06116.00 ± 14.06116.53 ± 12.22114.86 ± 6.930.605DBP (mmHg)71.00 ± 8.0669.89 ± 8.7470.93 ± 8.3571.21 ± 7.840.880PP (mmHg)47.50 ± 11.4946.11 ± 12.7442.75 ± 14.4243.64 ± 8.730.841Weight (kg)72.14 ± 14.3172.44 ± 15.4072.50 ± 14.9470.14 ± 13.090.924 IMAGING AND BIOMARKERS DURING CHEMOTHERAPYVariableBaselineAfter 2nd Cycle of Chemotherapy2 Weeks After Last Cycle of Chemotherapy6 Months After Last Cycle of ChemotherapyP VALUECARDIAC MRI PARAMETERS     EDV (ml/m2)71.03 ± 10.9775.10 ± 10.3476.03 ± 10.8574.74 ± 12.610.070ESV (ml/m2)25.78 ± 6.6328.83 ± 5.3330.82 ± 5.2429.75 ± 6.890.000      EDV (ml)124.73 ± 20.25133.13 ± 22.83136.21 ± 22.20132.214 ± 19.330.035ESV (ml)45.16 ± 11.8851.044 ± 11.0455.09 ± 10.0752.57 ± 11.650.000      MM(at ED) (gm)73.06 ± 11.5172.93 ± 18.1269.90 ± 13.8869.21 ± 15.130.827MM(at ED) (g/m2)41.64 ± 6.7441.11 ± 9.1538.79 ± 5.4938.61 ± 6.650.603            EF (%) (CARDIAC MRI)64.15 ± 5.3061.71 ± 4.3459.37 ± 4.6460.41 ± 5.770.000EF (%) (BIPLANE 2D ECHOCARDIOGRAM)65.38 ± 7.4266.55 ± 6.4061.86 ± 4.8260.57 ± 6.150.051      BIOMARKERS     Troponin I (ng/mL)0.012 ± 0.010.015 ± 0.020.015 ± 0.010.019 ± 0.040.312NTproBNP (pg/L)45.73 ± 49.8940.60 ± 35.8754.91 ± 59.2436.71 ± 32.370.704CRP (mg/L)3.707 ± 4.505.28 ± 6.425.64 ± 10.513.06 ± 4.110.324 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-11.</jats:p

OT1-02-12: Early Detection of Cardiotoxicity by Advanced Cardiac Imaging and a Novel Biomarker in Breast Cancer Patients Undergoing Chemotherapy.

Abstract Background The survival rate of breast cancer patients has increased due to improvements in cancer treatment. However, many survivors develop irreversible or reversible cardiotoxicity associated with anthracycline or trastuzumab therapy, respectively. To detect cardiac damage, the currently accepted method is to measure left ventricular ejection fraction (LVEF) by echocardiography, which lacks the sensitivity to predict early cardiac dysfunction. Early identification of cardiotoxicity is essential to cancer survivors, as development of cardiomyopathy carries a worse outcome independent of cancer prognosis. Currently, there are no accepted guidelines for the early detection of myocardial injury. The use of cardiac biomarkers and more sensitive echocardiographic techniques have expanded options for monitoring, but have yet to reach a consensus. Hence, our study will evaluate the potential predictive value of novel cardiac biomarkers and advanced echocardiographic and cardiac magnetic resonance imaging (CMR) techniques to detect subclinical myocardial damage. Our findings may be applicable for monitoring new antineoplastic agents during food and drug administration (FDA) clinical trials. Trial Design Prospective cohort study with internal control of 20 patients newly diagnosed with breast cancer. The trial will assess endpoints at baseline, 2 weeks after initiation of therapy, and 2 weeks and 6 months after chemotherapy completion. 1. Primary Endpoint a. Decline in left ventricular ejection fraction assessed by CMR and 3D-echo not detected by conventional methods b. Presence of either myocardial fibrosis or edema detected by CMR c. Changes in myocardial deformation detected by echo or CMR strain d. Increase in cardiac biomarkers (Serum caspase-3 p17 peptide, Troponin I, B-type natriuretic peptide) and possible correlation with imaging parameters 2. Secondary Endpoint a. Development New York Heart Association class 1 to 4 symptoms b. Decrease in LVEF of ≥5% to ≤50% with or without symptoms Eligibility Criteria Inclusion Criteria: 1. Newly diagnosed stage I, II, or III breast cancer 2. Age between 18 and 75 years old. 3. Treatment with trastuzumab or anthracycline-based chemotherapy Exclusion Criteria: 1. History of cardiovascular disease 2. Pacemaker 3. History of mediastinal radiotherapy 4. Creatinine clearance &amp;lt;30 ml/min 5. Serum bilirubin &amp;gt;2.0 mg/dl, ALT and AST &amp;gt; 100 U/1) 6. Hypertension, uncontrolled &amp;gt;140/90 7. LVEF &amp;lt;55% per 2-D echocardiogram 8. Claustrophobia Specific Aims 1. Detect early myocardial injury. 2. Evaluate early predictors of left ventricular dysfunction. 3. Evaluate timing of monitoring during or post treatment Statistical Method This is a pilot study and 20 patients are required to reach statistical significance with 85% power. All values will be analyzed as mean±SD or n (%). Categorical indicators will be analyzed using nonparametric statistics such as Cochran's Q. Changes in imaging and biomarker parameters will be assessed using analysis of variance, while correlation between the two will be assessed using mixed models appropriate for binary outcome. Significance will be accepted at p ≤0.05 for all tests. Present accrual and target accrual Nine subjects are enrolled with a goal of 20. Contact for people interested in trial: 1. Dr. Erick Avelar, [email protected] 2. Dr. Susan Tannenbaum, [email protected] Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-12.</jats:p