Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium

Seferina, Shanly C.; Boer, Maaike de; Derksen, M. Wouter; Berkmortel, Franchette van den; Kampen, Roel J.W. van; Wouw, Agnès J. van de; Joore, Manuela A.; Peer, Petronella G. M.; Voogd, Adri C.; Tjan‐Heijnen, Vivianne C. G.

doi:10.1634/theoncologist.2015-0230

Cited by 39 publications

(27 citation statements)

References 34 publications

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“…[9] This clinical decision is further complicated by the fact that trastuzumab cardiotoxicity often develops early in the course of treatment, at a time when patients may have received 50% or less of the intended trastuzumab course for breast cancer treatment. [10,11] While the clinical significance or long-term sequelae of an asymptomatic LVEF decline remains poorly understood in the cardio-oncology setting, it is a leading cause of premature interruption of trastuzumab. [11] The rationale to withhold trastuzumab is based on the premise that an asymptomatic LVEF decline is a precursor that can lead to HF if additional trastuzumab is administered.…”

Section: Introductionmentioning

confidence: 99%

Cardiac outcomes of trastuzumab therapy in patients with HER2-positive breast cancer and reduced left ventricular ejection fraction

Hussain

Drill

Dang

et al. 2019

Breast Cancer Res Treat

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Purpose: Asymptomatic decline in left ventricular ejection fraction (LVEF) or heart failure (HF) occur in up to 25% of patients treated with trastuzumab and can result in incomplete breast cancer therapy. The cardiac safety of continuing trastuzumab in patients with asymptomatic LVEF decline is unknown. We report the cardiac outcomes of patients treated with trastuzumab after a significant asymptomatic LVEF decline. Methods: Patients with HER2-positive breast cancer and asymptomatic LVEF decline to < 50% during trastuzumab were identified from an institutional echocardiogram database. Cardiac events were defined as HF (New York Heart Association class III-IV) or cardiovascular death. Results: 60 patients were included; the median age was 54 years. In 23 patients who continued trastuzumab, 14 (61%) tolerated trastuzumab without a cardiac event, 6 (26%) developed worsening LVEF (range 25-42%) leading to trastuzumab discontinuation, and 3 (13%) developed a cardiac event (1 HF, 2 possible/probable cardiovascular deaths). In 37 patients with interrupted trastuzumab, 15 (41%) were re-challenged with trastuzumab after LVEF improved to > 50%, 21 (57%) were not re-challenged, and 1 (3%) developed HF. More patients in the continued trastuzumab group had metastatic disease (39% vs. 5%, p=0.002). The final LVEF after median follow-up of 633 days was similar between patients with trastuzumab continuation versus interruption (54% vs. 56%, p=0.29).

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Section: Introductionmentioning

confidence: 99%

Cardiac outcomes of trastuzumab therapy in patients with HER2-positive breast cancer and reduced left ventricular ejection fraction

Hussain

Drill

Dang

et al. 2019

Breast Cancer Res Treat

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“…Studies suggest that the first 3months of trastuzumab therapy account for most of the cardiotoxic events, and that cardiotoxicity occurring more than 6months after start of trastuzumab is rare [32,33]. A Dutch study which included 230 patients treated with trastuzumab found that 84.8% of the patients who discontinue the drug due to cardiotoxicity do so in the first six months, and that the first LVEF drop was seen at a median of 2.5 months (range: 0.7-10.3 months) [1]. Our results shows that all events of LV dysfunction occurred in the first 6 months, and none of the patients who continued trastuzumab develops decline in LVEF even after 3 years of continuous treatment suggesting that trastuzumab cardiotoxicity is not dose dependent, and that cardiac monitoring should focus on the first year of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of the HER2 protein (a transmembrane tyrosine kinase receptor involved in cell differentiation and proliferation), amplification of the HER2 gene, or both occur in approximately 15 to 20 percent of breast cancers [1,2]. Trastuzumab is a humanized monoclonal antibody with specificity for the extracellular domain of HER-2 [3].…”

Section: Introductionmentioning

confidence: 99%

Left Ventricular Dysfunction in Breast Cancer Patients Receiving Trastuzumab: An Observational Study in a Cohort of Iraqi Breast Cancer Patients

2019

University of Thi-Qar Journal of Medicine

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Background : Cardiotoxicity is a well recognized adverse event of trastuzumab. This study was designed to evaluate the frequency of decline in left ventricular ejection fraction (LVEF) to less than 50% in patients with breast cancer who have received trastuzumab in a daily practice setting. Methods : Retrospective observational study of 116 patients with HER2 positive breast cancer treated with trastuzumab in one center between May 2012 and January 2017. Results : Left ventricular ejection fraction decline to less than 50% was observed in 7 patients (6%). Patients above 70 years of age have the highest frequency of LVEF decline (33%). All events of LVEF decline was reported in the first six months of treatment. Prolonged administration of trastuzumab beyond one year was not associated with adverse cardiac events. Previous anthracycline exposure and chest irradiation was not found to be associated with LVEF decline. Conclusions : Events of LVEF decline to less than 50% associated with trastuzumab use seems to be slightly higher in general daily practice than in clinical trial setting, especially in patients above 70 years, calling for better patient selection. First year of trastuzumab therapy carries the highest risk of cardiac events which necessitates a close cardiac monitoring, thereafter, periodic LVEF measurements can be reduced to reduce the costs.

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“…Currently, guidelines for cardiac surveillance recommend an EF evaluation before and during trastuzumab therapy (Mackey et al, 2008;Dang et al, 2016;Armenian et al, 2017), in particular in cases of early cardiotoxicity (Yu et al, 2015a;Seferina et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity: Impact on Adherence and Clinical Outcome

et al. 2020

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Background: Treatment with Trastuzumab is associated with cardiotoxicity. If Trastuzumab could be administered in a safe manner to patients who develop a reduced left ventricular ejection fraction (EF) of < 50% remains poorly understood. Objective: To evaluate the impact of a cardioncological approach in terms of adherence and continuation of oncological therapy with Trastuzumab. Methods and Results: Internal databases of candidates for trastuzumab chemotherapy with evidence of cardiotoxicity according to echocardiographic criteria were retrospectively evaluated. Eighty-four female patients (age 51.7 years, 95% CI 49.5-53.8), were finally included. Patients were divided to receive a standard (n 27) or cardioncological (n 57) scheme. Baseline EF values were within normal limits (60.9, 95% CI 60-61.9%; p=0.5 between groups). The nadir of EF observed during trastuzumab therapy was more pronounced in the standard care group (40.6, 95% CI 37.3-43.9% vs. 46.3, 95% CI 44.3-48.3%; p=0.002). At re-challenge, after cardiotoxicity detection, all patients in the cardioncological arm resumed and completed trastuzumab therapy (p<0.0001). An overall reduction of EF was observed at the final evaluation (p <0.0001 vs. baseline). Cardioncological approach was the only independent determinant of DEF from baseline to final evaluation (R 2 0.12; p=0.004). We observed a total of 13 (15%) HF events, seven (26%) in the standard, and six (10%) in the cardioncological approach group (p =0.1). Patients in the cardioncological approach arm had a better outcome (Log Rank Chi-squared 4.89; p=0.02). Conclusions: A targeted cardioncological approach, in patients with evidence of cardiotoxicity during HER-2 inhibitor therapy, could favorably influence the oncological management of breast cancer patients, reducing the adverse cardiovascular impact of chemotherapy.

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Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium

Cited by 39 publications

References 34 publications

Cardiac outcomes of trastuzumab therapy in patients with HER2-positive breast cancer and reduced left ventricular ejection fraction

Cardiac outcomes of trastuzumab therapy in patients with HER2-positive breast cancer and reduced left ventricular ejection fraction

Left Ventricular Dysfunction in Breast Cancer Patients Receiving Trastuzumab: An Observational Study in a Cohort of Iraqi Breast Cancer Patients

Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity: Impact on Adherence and Clinical Outcome

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