Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

Bouwer, Nathalie I; Steenbruggen, Tessa G; Rosmalen, Joost van; Rier, Hánah N.; Kitzen, Jos; Bekkum, Marlies L. van; Tije, Albert J. ten; Jong, P.C. de; Drooger, Jan C.; Holterhues, Cynthia; Smorenburg, Carolien H.; Kofflard, Marcel; Boersma, Eric; Sonke, Gabe S.; Levin, Mark‐David; Jager, Agnes

doi:10.1007/s10549-020-06039-w

Cited by 16 publications

(11 citation statements)

References 31 publications

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“…In our study, LVD occurred more commonly during the first 4 years of therapy. Our data agree with previous studies on MBC patients [17][18][19][22][23][24] who have documented a higher incidence of CTOX during the first years of treatment. Indeed, CTOX during prolonged trastuzumab therapy showed a plateau phenomenon characterized by a relatively early start of LVD.…”

Section: Discussionsupporting

confidence: 93%

Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction

Perone

Auñón²,

Rodríguez

et al. 2022

Monaldi Arch Chest Dis

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Trastuzumab therapy has dramatically changed breast cancer prognosis. Consensus documents recommend a close monitoring during therapy, not always feasible, especially in metastatic breast cancer. The purpose of this study is to describe trastuzumab cardiotoxicity in metastatic breast cancer patients to understand how to improve cardiovascular monitoring. We retrospectively studied metastatic breast cancer patients scheduled for trastuzumab therapy (2001-2018). All patients underwent a baseline evaluation and monitoring during therapy. Cardiotoxicity was defined as symptomatic heart failure or asymptomatic decrease in left ventricular ejection fraction > 10% from baseline and < 53%. Ninety-two women were included, mean age 61 years (±14.43), median follow-up 42.5 months (IQR 26-74). Fourteen percent developed cardiotoxicity: two heart failure with preserved left ventricular ejection fraction, three heart failure with reduced left ventricular ejection fraction, and eight asymptomatic decreased in left ventricular ejection fraction. Eighty-one percent of cardiac dysfunction cases occurred within the first 4 years and on median of 31 months from trastuzumab initiation. Thus, in metastatic breast cancer patients, trastuzumab-mediated cardiotoxicity occurred more frequently during the first 4 years. These data should be considered to optimize follow-up protocols.

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Section: Discussionsupporting

confidence: 93%

Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction

Perone

Auñón²,

Rodríguez

et al. 2022

Monaldi Arch Chest Dis

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“…In our cohort, older age and longer duration of trastuzumab-based therapy were predictive of CEs however given the borderline statistical significance (HR = 1.01) these results should be interpreted with caution when considering frequency of cardiac monitoring. Our results are consistent with findings from the Dutch group which observed that older age and a baseline reduced LVEF increased the risk of severe cardiotoxicity ( 21 ).…”

Section: Discussionsupporting

confidence: 93%

“…In this retrospective population-based study of HER2 + aBC, the incidence of cardiac events during or after trastuzumab-based therapy was 7.3%, ( n = 167) with heart failure representing the majority of these events (6.9%, n = 158). These findings are similar to the 3–7% reported in the literature ( 6 , 8 , 14 ), but lower than a Dutch study of 429 patients likely given the reported combined incidence of severe and non-severe cardiotoxicity based on LVEF parameters of 11.7% and 9.1% after 1 and 2 years of trastuzumab respectively ( 21 ); after 4 years of treatment, the cumulative incidence of severe cardiotoxicity (LVEF < 40%) was 3.1%.…”

Section: Discussionsupporting

confidence: 83%

Cardiac Monitoring and Heart Failure in Advanced Breast Cancer Patients Treated With Trastuzumab in Ontario, Canada

Rushton

Kappel

Lima

et al. 2022

Front. Cardiovasc. Med.

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BackgroundTrastuzumab has improved patient outcomes in HER2 + breast cancer (BC) but carries a risk of cardiotoxicity. Routine cardiac imaging is recommended for advanced breast cancer (aBC) patients during trastuzumab treatment despite a lack of evidence that this improves patient outcomes. This study was conducted to understand predictive factors for cardiac events and determine the impact of cardiovascular monitoring in aBC.MethodsThis retrospective population-based cohort study included aBC patients treated with trastuzumab (all lines), in Ontario, Canada from 2007 to 2017. The overall cohort was divided into two groups; those who developed a cardiac event (CE) vs. those who did not. Patients with pre-existing heart disease were excluded. Logistic regression was performed to identify patient characteristics associated with an increased risk of CE.ResultsOf 2,284 patients with HER2 + aBC treated with trastuzumab, 167 (7.3%) developed a CE. Median age at first dose of trastuzumab was 57 (IQR 49–66); 61 (IQR 51–70) for patients with a CE. Median number of cycles was 16 (IQR 7–32); 21 (IQR 8–45) for patients with a CE (p < 0.01). Twelve (0.5%) patients died of cardiac causes; all had a prior CE. Increased risk of CEs was associated with age > 60 (OR 5.21, 95% CI 1.83–14.84, p = 0.05) and higher number cycles of trastuzumab (OR 1.01; 95% CI 1–101, p = 0.028).ConclusionThis is the first population-based study to report on CEs and cardiac monitoring in HER2 + aBC patients during trastuzumab-based therapy. Older age and longer treatment with trastuzumab were associated with an increased risk of a CE.

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“…Adapting the surveillance approach and frequency according to risk stratification would be expected to reduce the frequency or even omit long-term follow-up in selected very low-risk patients. Bouwer et al investigated cardiotoxicity during long-term trastuzumab use in breast cancer patients, and found that in nonsmoking patients with baseline LVEF >60% and without cardiotoxicity during trastuzumab treatment, the cumulative incidence of severe cardiotoxicity was low, and that serial cardiac monitoring could be omitted safely (35). Thus, using current multiple treatment modalities related to CV toxicity, a CO team could identify who does or does not need cardiac monitoring, and improve the use of clinical resources.…”

Section: Discussionmentioning

confidence: 99%

Initial experience of the implementation of a cardio-oncology program for breast cancer patients receiving modern radiotherapy in a tertiary institution

Hou¹,

Wu²,

Wu³

et al. 2021

Ther Radiol Oncol

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Background: The modern era of multimodality cancer treatment strategies has contributed to a much longer survival time of breast cancer patients. Accordingly, cardiovascular toxicity related to anticancer therapy including radiation-induced heart disease has become an issue of concern. To address this issue, it is important to develop cardio-oncology programs to provide cardiovascular assessment, surveillance and management for patients receiving cancer therapy with potential heart impairment.Methods: A multidisciplinary cardio-oncology combined care team and clinical protocol were established.Cardiac assessments of patients at risk before radiation, and surveillance and management of cardiotoxicity after completing cancer therapy were performed. A novel radiotherapy planning technique with completedirectional-complete block in helical tomotherapy was used to reduce cardiac exposure dose and limit heart damage. We analyzed the effect in the patients receiving this modern technique and cardio-oncology care. Results:The number of breast cancer patients receiving cardio-oncology care increased annually, from 64 (71.9%) in 2013 to 177 (81%) in 2019. A series of cardiac assessments were performed, including cardiac biomarkers, electrocardiogram, echocardiogram, and/or myocardial perfusion imaging to evaluate the patient's cardiac risk or development of subsequent cardiotoxicity after cancer therapy. Among the 303 patients who were treated with the modern radiotherapy technique, 15 (5%) were diagnosed with cardiovascular disease by the combined care program.Conclusions: For the breast cancer patients receiving multimodality cancer treatment with modern radiotherapy in this study, the multidisciplinary cardio-oncology program of screening, prevention, management and follow-up protocols reduced cancer therapy-related cardiovascular toxicity, and improved the clinical outcomes and quality of life for long-term survivors.

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Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

Cited by 16 publications

References 31 publications

Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction

Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction

Cardiac Monitoring and Heart Failure in Advanced Breast Cancer Patients Treated With Trastuzumab in Ontario, Canada

Initial experience of the implementation of a cardio-oncology program for breast cancer patients receiving modern radiotherapy in a tertiary institution

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