Segmental Left Ventricular Longitudinal Strain Changes Following Tangential Radiation in Left-Sided Breast Cancer Patients

Abstract Background Echocardiographic global longitudinal strain (GLS) detects early subclinical left ventricular (LV) systolic dysfunction, before the occurrence of a decreased LV ejection fraction. However, our local data is lacking to determine its impact to clinical outcomes. Purpose The study aimed to determine the clinical outcomes of breast cancer patients who developed subclinical LV systolic dysfunction as determined by an abnormal GLS post-chemotherapy. Methods This retrospective cohort study included 99 breast cancer patients who underwent anthracycline and/or HER-2 receptor inhibitor chemotherapy from January 1, 2016 to December 31, 2018 in a single tertiary hospital. Clinical outcomes of all-cause mortality and overt heart failure were compared between those with normal and abnormal GLS post-chemotherapy. Results The prevalence of subclinical LV systolic dysfunction was 18%, wherein 28% of them had subsequent overt heart failure, and 33% expired. Abnormal GLS occurred at a mean 3.5 months (range 1–8 months) after initiation of chemotherapy and at 8 months (range 6–10 months) after the entire chemotherapy sessions. Development into heart failure was observed at a mean of 6.7 months (range 4–12 months) after occurrence of abnormal GLS. Hypertension and age >56 years were determined to be risk factors. Beta-blockers, ACE inhibitors and statins seemed to be non-protective in our cohort. Abnormalities in GLS were observed at a mean dose of 260 mg/m2 of epirubicin, lower than the dose described as high risk in the literature (600 mg/m2 for epirubicin). In trastuzumab, abnormal GLS occurred as early as 1 month after initiation. LVEF had no significant change within 2 months (p=0.56), but was significantly lower within 12 months post-chemotherapy (p=0.005). All-cause mortality was 3-fold higher (RR=3.00; p=0.02), and the risk to develop heart failure was 4 times higher (RR=4.74; p=0.008) in those with abnormal GLS. Conclusion The development of abnormal GLS post-chemotherapy was associated with subsequent development of overt heart failure and increased all-cause mortality. Abnormal GLS occurred at lower doses of epirubicin and as early as 1 month after initiating trastuzumab. We recommend echo surveillance with GLS monitoring beginning >250 mg/m2 with anthracycline (and after 1–2 months of Trastuzumab), and to repeat at 1–2 months and 9–12 months post-chemotherapy. Funding Acknowledgement Type of funding source: None

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Fully automated and comprehensive MRI-based left-ventricular contractility analysis in post-chemotherapy breast cancer patients

British Journal of Radiology ◽

10.1259/bjr.20190289 ◽

2020 ◽

Vol 93 (1105) ◽

pp. 20190289

Author(s):

Julia Kar ◽

Michael V. Cohen ◽

Samuel A. McQuiston ◽

Maria S. Figarola ◽

Christopher M. Malozzi

Keyword(s):

Breast Cancer ◽

Steady State ◽

Cancer Patients ◽

Healthy Subjects ◽

Longitudinal Strain ◽

Steady State Free Precession ◽

Left Ventricular ◽

Free Precession ◽

Breast Cancer Patients ◽

Basal Diameter

Objective: This study investigated the occurrence of cardiotoxicity-related left-ventricular (LV) contractile dysfunction in breast cancer patients following treatment with antineoplastic chemotherapy agents. Methods: A validated and automated MRI-based LV contractility analysis tool consisting of quantization-based boundary detection, unwrapping of image phases and the meshfree Radial Point Interpolation Method was used toward measuring LV chamber quantifications (LVCQ), three-dimensional strains and torsions in patients and healthy subjects. Data were acquired with the Displacement Encoding with Stimulated Echoes (DENSE) sequence on 21 female patients and 21 age-matched healthy females. Estimates of patient LVCQs from DENSE acquisitions were validated in comparison to similar steady-state free precession measurements and their strain results validated via Bland–Altman interobserver agreements. The occurrence of LV abnormalities was investigated via significant differences in contractility measurements (LVCQs, strains and torsions) between patients and healthy subjects. Results: Repeated measures analysis showed similarities between LVCQ measurements from DENSE and steady-state free precession, including cardiac output (4.7 ± 0.4 L, 4.6 ± 0.4 L, p = 0.8), and LV ejection fractions (59±6%, 58±5%, p = 0.2). Differences found between patients and healthy subjects included enlarged basal diameter (5.0 ± 0.5 cm vs 4.4 ± 0.5 cm, p < 0.01), apical torsion (6.0 ± 1.1° vs 9.7 ± 1.4°, p < 0.001) and global longitudinal strain (−0.15 ± 0.02 vs. -0.21 ± 0.04, p < 0.001), but not LV ejection fraction (59±6% vs. 63±6%, p = 0.1). Conclusion: The results from the statistical analysis reveal the possibility of LV abnormalities in the post-chemotherapy patients via enlarged basal diameter and reduced longitudinal strain and torsion, in comparison to healthy subjects. Advances in knowledge: This study shows that subclinical LV abnormalities in post-chemotherapy breast cancer patients can be detected with an automated technique for the comprehensive analysis of contractile parameters.

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Abstract P345: A MRI Displacement-based Deep-learning Semantic Segmentation Tool For Left-ventricular Longitudinal Strain Analysis In Cardiotoxicity

Circulation Research ◽

10.1161/res.129.suppl_1.p345 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Julia Kar ◽

Michael V Cohen ◽

Teja Poorsala ◽

Samuel A McQuiston ◽

Cheri Revere ◽

...

Keyword(s):

Breast Cancer ◽

Deep Learning ◽

Cancer Patients ◽

Healthy Subjects ◽

Longitudinal Strain ◽

Strain Analysis ◽

Semantic Segmentation ◽

Left Ventricular ◽

Phase Unwrapping ◽

Breast Cancer Patients

Global longitudinal strain (GLS) computed in the left-ventricle (LV) is an established metric for detecting cardiotoxicity in breast cancer patients treated with antineoplastic agents. The purpose of this study was to develop a novel, MRI-based, deep-learning semantic segmentation tool that automates the phase-unwrapping for LV displacement computation in GLS. Strain analysis via phase-unwrapping was conducted on 30 breast cancer patients and 30 healthy females acquired with the Displacement Encoding with Stimulated Echoes (DENSE) sequence. A ResNet-50 deep convolutional neural network (DCNN) architecture for automated phase-unwrapping, a previously validated ResNet-50 DCNN for chamber quantification and the Radial Point Interpolation Method were used for GLS computation (Figure 1). The DCNN's performance was measured with F1 and Dice scores, and validated in comparison to the robust transport of intensity equation (RTIE) and quality guided phase-unwrapping (QGPU) conventional algorithms. The three techniques were compared by intraclass correlation coefficient with Cronbach’s alpha (C-alpha) index. Classification accuracy with the DCNN was F1 score of 0.92 and Dice score of 0.89. The GLS results from RTIE, QGPU and DCNN were -16.0 ± 2%, -16.1 ± 3% and -15.9 ± 3% (C-alpha = 0.89) for patients and -18.9 ± 3%, -19.0 ± 4% and -18.9 ± 3% (C-alpha = 0.92) for healthy subjects. Comparable validation results from the three techniques show the feasibility of a DCNN-based approach to LV displacement and GLS analysis. The dissimilarities between patients and healthy subjects demonstrate that DCNN-based GLS computation may detect LV abnormalities related to cardiotoxicity.

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

Cardio-Oncology ◽

10.1186/s40959-021-00103-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jennifer K. Lang ◽

Badri Karthikeyan ◽

Adolfo Quiñones-Lombraña ◽

Rachael Hageman Blair ◽

Amy P. Early ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Care Center ◽

Left Ventricular ◽

The Body ◽

Left Ventricular Ejection ◽

Breast Cancer Patients ◽

Ventricular Ejection Fraction ◽

Echocardiographic Parameters ◽

The Impact

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

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

Clinics and Practice ◽

10.3390/clinpract11030064 ◽

2021 ◽

Vol 11 (3) ◽

pp. 484-493

Author(s):

Jukapun Yoodee ◽

Aumkhae Sookprasert ◽

Phitjira Sanguanboonyaphong ◽

Suthan Chanthawong ◽

Manit Seateaw ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Cancer Patients ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Breast Cancer Patients ◽

Ventricular Ejection Fraction ◽

Factors Associated ◽

Palliative Intent ◽

Increased Risk

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

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Immediate evaluation of global longitudinal strain at initiation of trastuzumab treatment in breast cancer patients

Echocardiography ◽

10.1111/echo.15190 ◽

2021 ◽

Author(s):

Ann Banke ◽

Morten Schou ◽

Marianne Ewertz ◽

Jordi Dahl ◽

Peter Hartmund Frederiksen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Longitudinal Strain ◽

Global Longitudinal Strain ◽

Breast Cancer Patients ◽

Trastuzumab Treatment

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Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.1611 ◽

2007 ◽

Vol 25 (25) ◽

pp. 3859-3865 ◽

Cited By ~ 378

Author(s):

Thomas M. Suter ◽

Marion Procter ◽

Dirk J. van Veldhuisen ◽

Michael Muscholl ◽

Jonas Bergh ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Effects ◽

Cancer Patients ◽

Cardiac Dysfunction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Breast Cancer Patients ◽

Ventricular Ejection Fraction ◽

Neo Adjuvant Chemotherapy

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

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Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients

Breast Care ◽

10.1159/000513766 ◽

2021 ◽

pp. 1-7

Author(s):

Christoph Suppan ◽

Daniel Steiner ◽

Eva Valentina Klocker ◽

Florian Posch ◽

Elisabeth Henzinger ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Safety And Efficacy ◽

Her2 Positive Breast Cancer ◽

Tumor Stages ◽

Positive Breast Cancer

Background: The addition of trastuzumab to standard chemotherapy has improved survival in patients with HER2-positive breast cancer in neoadjuvant, adjuvant, and metastatic settings. In higher tumor stages, the addition of pertuzumab is now a standard of care and associated with a favorable toxicity profile. We evaluated the safety and efficacy of the trastuzumab biosimilar SB3 in combination with pertuzumab in HER2-positive breast cancer patients. Methods: Seventy-eight patients with HER2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz were included. Summary measures are reported as medians (25th to 75th percentile) for continuous variables and as absolute frequencies (%) for count data. Results: Thirty-five patients received a median of 4 (3–7) cycles of trastuzumab biosimilar SB3 plus pertuzumab. All patients had a normal baseline left ventricular ejection fraction (LVEF; >50%) prior to the initiation of SB3 plus pertuzumab treatment with a median LVEF of 60% (60–65). Twenty-one patients had a median absolute LVEF decline of 1% (–5 to 0). Two patients (5.7%) had a LVEF reduction ≤50%, but none ≥10%. There were no unexpected adverse events. Twenty-two of 35 patients (63%) were treated with trastuzumab biosimilar SB3 and pertuzumab in the neoadjuvant setting and 11 patients (50%) achieved a pathological complete response. The safety and the efficacy in this setting was comparable to the trastuzumab plus pertuzumab combination in neoadjuvantly treated matched samples. Conclusion: In this series of HER2-positive breast cancer patients, the combination of SB3 plus pertuzumab was consistent with the known safety and efficacy profile of trastuzumab and pertuzumab combination.

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