Epirubicin and long‐term heart failure risk in breast cancer survivors

Mahmood, Syed; Patel, Ravi B.; Butler, Javed; Vaduganathan, Muthiah

doi:10.1002/ejhf.1215

Cited by 8 publications

(6 citation statements)

References 15 publications

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“…This observation suggested that the risk of treatment-associated heart failure may be multifactorial; the risk of anthracycline-induced cardiac dysfunction needs to be noted when patients who were under the circumstance of a high dosage of left-sided breast irradiation. Although epirubicin has been announced with a low cardiac toxicity profile ( 20 , 21 ), epirubicin-associated heart failure is still a concern in breast cancer survivors ( 22 , 23 ). A 20-year follow-up study indicated that the cumulative incidence of heart failure was higher (up to a three-fold increased risk) in the epirubicin treatment group when compared with the non-epirubicin group ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study

Lee

Tsai

Yang³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundEven though advanced radiotherapy techniques provide a better protective effect on surrounding normal tissues, the late sequelae from radiation exposure to the heart are still considerable in breast cancer patients. The present population-based study explored the role of cox-regression-based hazard risk grouping and intended to stratify patients with post-irradiation long-term heart diseases.Materials and methodsThe present study investigated the Taiwan National Health Insurance (TNHI) database. From 2000 to 2017, we identified 158,798 breast cancer patients. Using a propensity score match of 1:1, we included 21,123 patients in each left and right breast irradiation cohort. Heart diseases, including heart failure (HF), ischemic heart disease (IHD), and other heart diseases (OHD), and anticancer agents, including epirubicin, doxorubicin, and trastuzumab, were included for analysis.ResultsPatients received left breast irradiation demonstrated increased risks on IHD (aHR, 1.16; 95% CI, 1.06–1.26; p < 0.01) and OHD (aHR, 1.08; 95% CI, 1.01–1.15; p < 0.05), but not HF (aHR, 1.11; 95% CI, 0.96–1.28; p = 0.14), when compared with patients received right breast irradiation. In patients who received left breast irradiation dose of >6,040 cGy, subsequent epirubicin might have a trend to increase the risk of heart failure (aHR, 1.53; 95% CI, 0.98–2.39; p = 0.058), while doxorubicin (aHR, 0.59; 95% CI, 0.26–1.32; p = 0.19) and trastuzumab (aHR, 0.93; 95% CI, 0.33–2.62; p = 0.89) did not. Older age was the highest independent risk factor for post-irradiation long-term heart diseases.ConclusionGenerally, systemic anticancer agents are safe in conjunction with radiotherapy for managing post-operative breast cancer patients. Hazard-based risk grouping may help stratify breast cancer patients associated with post-irradiation long-term heart diseases. Notably, radiotherapy should be performed cautiously for elderly left breast cancer patients who received epirubicin. Limited irradiation dose to the heart should be critically considered. Regular monitoring of potential signs of heart failure may be conducted.

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Section: Discussionmentioning

confidence: 99%

Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study

Lee

Tsai

Yang³

et al. 2023

Front. Cardiovasc. Med.

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“…Generally, the DNA methylation status in cells can be influenced by disease progression [24] and drug treatment [25]. EPI is a popular chemotherapeutic agent with cardiotoxic adverse effects [17]. Although different studies have investigated the impact of EPI on cellular mechanisms at RNA [26] and protein [27] levels, there is not much research on the epigenetic effect of EPI, especially on DNA methylation level.…”

Section: Discussionmentioning

confidence: 99%

“…The MeDIP-seq data used in this study was extracted from cardiac microtissues exposed to epirubicin (EPI). While EPI is an important anticancer agent, it can cause short-term heart failure at a very high dose (around 900 mg/m2) and substantial cardiotoxicity at lower doses [17]. By analyzing the methylation status of cardiac tissues exposed to EPI, we identified candidate genes that had strong DNA methylation alteration related to the EPI-induced mechanism.…”

Section: Introductionmentioning

confidence: 99%

A bioinformatics workflow to detect genes with DNA methylation alterations: a case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin

Nguyen

Lienhard

Herwig

et al. 2022

2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics

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Epigenetic modification such as DNA methylation can be influenced by different exposure conditions. Alterations in DNA methylation status can then lead to changes in gene and protein expressions. Therefore, studying DNA methylation is needed to provide a comprehensive view of cellular mechanisms. One of the costeffective technologies to detect DNA methylation is methylated DNA immunoprecipitation-sequencing (MeDIP-seq). While some tools have been developed to analyze the MeDIP-seq data, they mainly focus on methylated genome regions. Thus, there is still a demand for an analysis process that can detect genes with significant differential methylation. In this study, we developed a workflow built on the QSEA package, a recent launched MeDIP-seq analysis tool in R, to analyze DNA methylation at gene levels. This workflow offers an approach to identify candidate genes with strong methylation alterations. We applied this workflow to analyze MeDIP-seq data from cardiac tissues exposed to epirubicin (EPI), which is an antitumor agent with cardiotoxic adverse effects. Several genes that had strong methylation alteration such as HDAC4, EHMT1, SNHG14, SDHA, IGF1R, ADAP1, and NCOR2, were determined and can be candidates for further EPI-induced cardiotoxicity investigation.

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“…The prevalence of symptomatic heart failure previously reported in patients receiving epirubicin-based regimens ranges from 1 to 8% for small doses of epirubicin not exceeding 500 mg/m 2 [ 10 – 12 ]. In patients receiving higher cumulative doses (≥900 mg/m 2 ), symptomatic CTRCD prevalence may exceed 5 to 10% [ 11 ]. The small number of patients presenting with symptomatic heart failure in our study (3%) is mainly due to our patients' selection criteria.…”

Section: Discussionmentioning

confidence: 99%

The Predictive Value of 2D Myocardial Strain for Epirubicin-Induced Cardiotoxicity

Abdallah

Nasr

Chourabi

et al. 2020

Journal of Oncology

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Introduction. Although epirubicin has significantly improved outcome in breast cancer (BC) patients, it is responsible for myocardial dysfunction that affects patients’ quality of life. The use of 2D global longitudinal strain (GLS) has been reported to detect early myocardial dysfunction. The aim of this study was to evaluate how GLS changes can predict cardiotoxicity. Methods. We conducted a prospective study from March 2018 to March 2020 on 66 patients with no cardiovascular risk factors, who presented with BC and received epirubicin. We measured left ventricular ejection fraction (LVEF) and GLS before chemotherapy, at three months (T3), and at 12 months (T12) from the last epirubicin infusion. Chemotherapy-Related-Cardiac-Dysfunction (CTRCD) was defined as a decrease of 10% in LVEF to a value below 53% according to ASE and EACI 2014 expert consensus. Results. The mean age at diagnosis was 47 ± 9 years old. At baseline, median LVEF was 70% and median GLS was −21%. Shortly after chemotherapy completion, two patients presented with symptomatic heart failure while asymptomatic CTRCD was revealed in three other patients at T12. Three months after the last epirubicin infusion, median LVEF was 65%, median GLS was −19%, and median GLS variation was 5%. However, in patients who presented with subsequent CTRCD, median GLS at T3 was −16% and median GLS variation was 19% ( p = 0.002 and p < 0.001 , respectively, when compared to patients who did not develop cardiotoxicity). Persistent GLS decrease at T3 was an independent predictor of CTRCD at T12. Age and left-sided thoracic irradiation did not increase the risk of cardiotoxicity in our study while the cumulative dose of epirubicin significantly affected cardiologic findings ( p = 0.001 ). Conclusion. This was the first North African study that assesses the value of measuring GLS to early detect cardiotoxicity. Patients whose GLS remained decreased after 3 months from anthracyclines-base chemotherapy had an increased risk for developing subsequent CTRCD. Further studies with larger sample size are warranted to identify the best cardioprotective molecules to be initiated in these patients before LVEF declines.

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Epirubicin and long‐term heart failure risk in breast cancer survivors

Cited by 8 publications

References 15 publications

Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study

Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study

A bioinformatics workflow to detect genes with DNA methylation alterations: a case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin

The Predictive Value of 2D Myocardial Strain for Epirubicin-Induced Cardiotoxicity

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