Left ventricular function following adjuvant chemotherapy for breast cancer: The NCIC CTG MA5 experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 522-522 ◽  
Author(s):  
L. E. Shepherd ◽  
W. Parulekar ◽  
K. I. Pritchard ◽  
M. Trudeau ◽  
N. Paul ◽  
...  

522 Background: Cardiac toxicity associated with anthracylines and more recently herceptin used in adjuvant breast cancer treatment is well recognized. Little is known about long term cardiac function as measured by left ventricular ejection fraction (LVEF) in patients post therapy. We analyzed the database of a randomized Phase 3 NCIC CTG study to assess changes over time in LVEF. Methods: Between 1989–1993, 710 pre/perimenopausal patients with node positive breast cancer were allocated to receive CEF (cyclophosphamide (C) 75 mg/m2 po d 1–14, epirubicin (E) 60 mg/m2 IV and fluorouracil (F) 500mg/m2 IV d1,d8) or CMF (C 100mg/m2 po d1–14, methotrexate (M) 40mg/m2 and F 600mg/m2 IV d1,8) given every 28 days for 6 cycles. The 10 year relapse-free survival was 52% (CEF) vs 45% (CMF), HR 1.31; stratified log rank, P=.007 (JCO, 2005,23;5166). LVEF was measured on both arms at baseline, months 6, 12, 36, and 60. Results: Compliance was good with measurements available on 100% of women at baseline, and 39% and 40% of patients at 60 months on the CEF and CMF arms respectively. Changes in LVEF from baseline are shown in the table . Conclusion: Changes in cardiac function as measured by a decrease in LVEF are not infrequent in patients after adjuvant therapy, even in the absence of anthracyclines. At 60 months, decreases of >10% were seen in up to 25% of patients receiving epirubicin administered at a cumulative dose of 720mg/m2 and in up to 10% of patients receiving CMF on whom measurements were available. The clinical significance of these findings needs to be assessed. Acknowledgements: This study was supported by funding from the Canadian Cancer Society through the National Cancer Institute of Canada and Pfizer Inc. [Table: see text] [Table: see text]

2021 ◽  
Vol 11 (18) ◽  
pp. 8336
Author(s):  
Pedro Antunes ◽  
Dulce Esteves ◽  
Célia Nunes ◽  
Anabela Amarelo ◽  
José Fonseca-Moutinho ◽  
...  

Background: we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of exercise training on cardiac function and circulating biomarkers outcomes among women with breast cancer (BC) receiving anthracycline or trastuzumab-containing therapy. Methods: PubMed, EMBASE, Cochrane Library, Web of Science and Scopus were searched. The primary outcome was change on left ventricular ejection fraction (LVEF). Secondary outcomes included diastolic function, strain imaging and circulating biomarkers. Results: Four RCTs were included, of those three were conducted during anthracycline and one during trastuzumab, involving 161 patients. All trials provided absolute change in LVEF (%) after a short to medium-term of treatment exposure (≤6 months). Pooled data revealed no differences in LVEF in the exercise group versus control [mean difference (MD): 2.07%; 95% CI: −0.17 to 4.34]. Similar results were observed by pooling data from the three RCTs conducted during anthracycline. Data from trials that implemented interventions with ≥36 exercise sessions (n = 3) showed a significant effect in preventing LVEF decline favoring the exercise (MD: 3.25%; 95% CI: 1.20 to 5.31). No significant changes were observed on secondary outcomes. Conclusions: exercise appears to have a beneficial effect in mitigating LVEF decline and this effect was significant for interventions with ≥36 exercise sessions.


2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
S Pacella ◽  
M Bonacina ◽  
S Morzenti ◽  
L Guerra ◽  
E De Ponti ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients undergoing chemotherapy (CHT) for breast cancer (BC) need a monitoring of cardiac function due to the possible onset of cardiotoxicity. Cardiotoxicity may occur with heart failure but is often asymptomatic and is detectable only by assessing an increase in cardiac volumes (left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes) and/or by a reduction of the left ventricular ejection fraction (LV-EF). The primary purpose of this study was to evaluate the role of gated SPECT myocardial perfusion imaging in this setting. Dosimetric evaluation was also assessed. Methods Seventeen BC patients (mean age 55.93 ± 11.04 years)with invasive ductal carcinoma HER2 + treated with surgery and with an anthracycline-based adjuvant CHT, were enrolled. The trend of cardiac function was assessed by evaluation of LV-EF, LV-EDV and LV-ESV using gSPECT in baseline conditions and at 12, 15 and 52 weeks during treatment and then at 6, 12, 24 and 48 months during follow-up. Each patient was studied 15-20 min after injection of 555 MBq of 99mTc-Tetrofosmin with gSPECT (16 frames/cardiac cycle) using an Infinia Hawkeye IV gamma-camera. Dosimetry was assed according to ICRP reports. Results Two out of the 17 patients enrolled left the protocol: one because of a second tumor and the other due to the appearance of cardiotoxicity. 15 patients completed the study: mean LVEF at baseline was 70.67 ± 5.68. The greatest modification occurred after 15th week of treatment, when mean LV-EF showed a significant decrease  to 65.67 ± 8.27, while mean LV-EDV and mean LV-ESV increased from 73.60 ± 16.72 up to 84.73 ± 21.11 and from 21.93 ± 7.17 up to 30.27 ± 14.16, respectively. All parameters progressively returned similar to baseline values at the final examination (after 48th month): mean LV-EF 70.20 ± 5.65, LV-EDV 73.40 ± 16.15 and ESV 22.07 ± 7.50. In one case cardiotoxicity occurred at 15th week: LV-EF decreased from 69 to 47%, LV-EDV increased from 92 up to 142 ml and LV-ESV from 28 up to 75 ml. According to our image protocols, effective dose for gSPECT was 3.83 mSv (ICRP 106). The use of gSPET instead of MUGA (6.47 mSv–ICRP 80) allowed a dose effective saving of 2.64 mSv/each control with a total saving of 21.12 mSv/patient. Conclusions Although the small sample size, gSPECT was demonstrated to be an applicable tool for monitoring cardiac  function because it correctly identified  BC patient with cardiotoxicity. gSPECT also allowed a significant radiation dose saving compared to MUGA: this is particularly relevant in cardiotoxicity studies that require repeated and close evaluations.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Steen ◽  
M Montenbruck ◽  
P Wuelfing ◽  
S Esch ◽  
A K Schwarz ◽  
...  

Abstract Background Cardiotoxicity during cancer treatment has become an acknowledged problem of chemotherapy medications and radiation therapy. Limitations of biomarkers and imaging tests such as echocardiography left ventricular ejection fraction (LVEF) hinder early detection of cardiotoxicity and proactive cardioprotective therapy. Once the heart is unable to compensate for subclinical dysfunction, systemic damage and remodeling occurs increasing the potential for heart failure. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. This study evaluates the ability of fSENC to detect subclinical cardiotoxicity and manage cardioprotective therapy in cancer patients. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the MyoStrain software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular & apical) with 16LV/6RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21LV/5RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxan therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Comparisons were made with paired t-Test with a 95% confidence interval. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. Figure 1 shows bar graphs of the % of normal LV myocardium (e.g. % LV MyoStrain Segments <−17%) at baseline and sequential follow-ups for patients without cardiotoxicity and with cardiotoxicity requiring cardioprotective therapy. Patients observing cardiotoxicity had a statistically significant decline in cardiac function measured by segmental fSENC (p=0.0002) which resolved after cardioprotective therapy. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical cardiotoxicity during chemotherapy and impact of cardioprotective therapy. The ability to serve as a surrogate safety endpoint for chemotherapy or other pharmacological agents, and aid management of cardiotoxicity by serving as a surrogate efficacy endpoint for cardioprotection agents, dosage, and patient compliance may help physicians detect subclinical cardiac dysfunction, and proactively manage cancer patients to avoid early or late heart failure.


2004 ◽  
Vol 22 (15) ◽  
pp. 3070-3079 ◽  
Author(s):  
Jacques Bonneterre ◽  
Henri Roché ◽  
Pierre Kerbrat ◽  
Pierre Fumoleau ◽  
Marie-Josèphe Goudier ◽  
...  

Purpose To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FEC 50) or the same regimen with epirubicin 100 mg/m2 (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group–05 trial. Patients and Methods One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. Conclusion After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection.


Author(s):  
John Satish Rudrapogu ◽  
Biju Govind ◽  
Adinarayana Unnagiri

Background: Anthracyclines are extensively used in the treatment of breast cancer. However, these therapeutic agents are responsible for chemotherapy-induced cardiotoxicity. Aim of this study was to assess the effect of use of prophylactic nebivolol for the prevention of anthracycline-induced cardiotoxicity in breast cancer patients.Methods: This was a prospective, randomized, single-blind, and placebo-controlled trial involving 80 participants with breast cancer, scheduled to undergo chemotherapy with doxorubicin. Patients were randomly divided into two groups: the nebivolol group (n=40) to receive nebivolol 5 mg daily and the placebo group (n=40) to receive placebo. All patients were evaluated with baseline Electrocardiogram (ECG) and echocardiography prior to treatment, and at the 6-month follow-up. Echocardiography included 2D echocardiography, colour doppler and tissue doppler imaging.Results: The study groups had comparable baseline echocardiographic variables. At the 6-month echocardiographic follow-up, there were no changes of statistical significance in any 2D echocardiographic variables in either group. However, there were minimal reductions of 0.4% in left ventricular ejection fraction in the nebivolol group (62.2±4.4% to 61.9±4.2%, p=0.75) and 1.6% in the placebo group (62.8±3.6% to 61.8±3.2%, p=0.18). Doppler examinations also did not reveal any statistically significant changes in variables such as peak A velocity, peak E velocity, E/A ratio, isovolumic relaxation time, and isovolemic contraction time in either group.Conclusions: Prophylactic use of nebivolol treatment may possess cardioprotective properties against anthracycline-induced cardiotoxicity in breast cancer patients although not statistically significant in this study.


2011 ◽  
Vol 93 (2) ◽  
pp. 127-129 ◽  
Author(s):  
Ron Shapiro ◽  
Daphna Barsuk ◽  
Lior Segev ◽  
Shani Shimon-Paluch ◽  
Haim Berkenstadt ◽  
...  

INTRODUCTION In patients receiving pre-operative anthracyclines for locally advanced breast cancer, early cardiotoxicity is a well-recognised complication that may interfere with surgery. The aim of this study was to assess the safety of breast surgery after neoadjuvant treatment with Doxorubicin. PATIENTS AND METHODS A retrospective study of breast cancer patients treated with Doxorubicin as part of their neoadjuvant protocol. All patients were subsequently operated in our institution. Intra-operative and postoperative haemodynamic, cardiac or respiratory events were collected. RESULTS A total of 83 patients were included. All patients had a normal left ventricular ejection fraction before starting on chemotherapy. Doxorubicin was given in conjunction with Cyclophosphamide and Paclitaxel. The cumulative dose of Doxorubicin was 240 mg/m2. All patients completed their chemotherapy less than a year before surgery and were clinically asymptomatic. Of the patients, 2.3% displayed a significant reduction in cardiac function to meet cardiotoxicity criteria, although not clinically apparent. No complications occurred intra-operatively or postoperatively. CONCLUSIONS Breast surgery can be safely performed after breast neoadjuvant chemotherapy with Doxorubicin. The risk of early cardiotoxicity does not mandate a cardiac function assessment after completion of treatment. Work-up should be individualised according to the anthracycline regimen, patient's cardiac risk factors and functional status before surgery.


2019 ◽  
Vol 8 (2) ◽  
pp. 254 ◽  
Author(s):  
Marco Mazzotta ◽  
Eriseld Krasniqi ◽  
Giacomo Barchiesi ◽  
Laura Pizzuti ◽  
Federica Tomao ◽  
...  

Trastuzumab is a milestone in the treatment of human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), in both the early and metastatic settings. Over the last two decades, clinical trials have established the good safety profile of trastuzumab. Cardiotoxicity remains the most frequent adverse event, more commonly exemplified by an asymptomatic decline in the left ventricular ejection fraction rather than congestive heart failure. Results from several long-term (>5 years) safety analyses have been recently published, with the inherent evidence substantially confirming the findings from previous trials. The clinical experience gained over the years in the use of trastuzumab has also fueled a number of observational studies focused on the effectiveness of this drug in the real-world settings. We herein reviewed the evidence available from tree major databases, namely, PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), to explore and critically discuss key issues related to the long-term safety and effectiveness of trastuzumab in clinical practice.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13009-e13009
Author(s):  
Jamal Zekri ◽  
Haleem J. Rasool ◽  
Syed Azhar J Rizvi ◽  
Ehab Mosaad Abdel Ghany Mahmoud ◽  
Ayman Ahamd Rasmy ◽  
...  

e13009 Background: Chemotherapy regimens (C) containing a combination of anti-Her2 antibodies are associated with a risk of cardiac toxicity in landmark clinical trials. We evaluate the cardiac function of patients with Her2 over-expressed (Her2OE) breast cancer (BC) receiving C combined with trastuzumab (T) and pertuzumab (P) in routine clinical practice setting. Methods: The initial cohort of patients who started C in combination with TP (CTP) in standard doses and schedules before September 2019 in 4 cancer units were included. All patients had regular measurement of left ventricular ejection fraction (LVEF) by Doppler ultrasound studies. Data was collected retrospectively and was limited to the first 24 months after initiation of CTP treatment. The paired sample T-test was used to test the significance of the difference in LVEF. Results: Sixty seven patients were identified. CTP treatment was administered in the neoadjuvant and palliative settings in 28 (41.8%) and 39 (58.2%) respectively. None of the patients received concomitant anthracycline with TP. All patients underwent LVEF assessment prior to starting CTP treatment and at 3 and 6 months later. Subsequently LVEF was measured at 9, 12, 15, 18, 21 and 24 months as long as patients are still receiving CTP treatment (table). LVEF was measured in 11 patients for 24 months. Compared to baseline, mean LVEF was not significantly different at any of the subsequent time points (range; decrease by -0.936% to increase by 1.087%) (Table). Dual anti-Her2 antibodies (TP) administration was omitted temporarily once for 2 patients due to clinically suspected cardiac toxicity which was excluded on further investigations. Conclusions: In this cohort describing our limited initial experience, dual anti-Her2 antibodies (T&P) combined with chemotherapy is not associated with significant cardiac toxicity when LVEF is measured every 3 months. Further studies investigating less frequent LVEF monitoring (e.g. every 5-6 months) may be warranted.[Table: see text]


2017 ◽  
Vol 35 (35) ◽  
pp. 3942-3948 ◽  
Author(s):  
Patricia A. Ganz ◽  
Edward H. Romond ◽  
Reena S. Cecchini ◽  
Priya Rastogi ◽  
Charles E. Geyer ◽  
...  

Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.


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