Acute Cardiotoxic Effects of Adjuvant Trastuzumab Treatment and its Relation to Oxidative Stress

Dirican, Ahmet; Levent, Fatih; Alacacıoğlu, Ahmet; Küçükzeybek, Yüksel; Varol, Umut; Kocabaş, Uğur; Şenöz, Oktay; Emre, Sadık Volkan; Demir, Lutfiye; Çoban, Eyüp; Aksun, Saliha; Sütçü, Recep; Tarhan, Mustafa Oktay

doi:10.1177/0003319714536602

Cited by 8 publications

(13 citation statements)

References 6 publications

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“…MPO is an enzyme secreted by polymorphonuclear leukocytes that is proatherogenic and prooxidant (20). It is believed to be a marker of oxidative stress (20), 1 of the central mechanisms of doxorubicin cardiotoxicity (21), as well as potentially related to ErbB2 inhibition by trastuzumab (22, 23). In our study, it is also possible that the MPO increases from doxorubicin persisted into the period when trastuzumab was administered.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab

et al. 2015

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BACKGROUND Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10–1.71), P = 0.02; PlGF 3.78 (1.30–11.0), P = 0.047; GDF-15 1.71 (1.15–2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.

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Section: Discussionmentioning

confidence: 99%

Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab

et al. 2015

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“…Some recent studies have suggested that trastuzumab-mediated cardiotoxicity may be a result of the accumulation of ROS which increased oxidative stress inside the cell, as a consequence of the blockage of the HER2 pathway. 12 The same study also suggested that, as erythroid cells may also express HER2 in their membranes, 13 this may also cause red blood cell death in vitro due to trastuzumab, which may lead to hemolytic crisis in patients with G6PD deficiency.…”

Section: Discussionmentioning

confidence: 96%

Safe neoadjuvant trastuzumab-based treatment in HER2 + inflammatory early breast cancer in a glucose 6-phosphate dehydrogenase-deficient postmenopausal woman: A case report and review of the literature

Cunquero-Tomás

Ávila-Andrade

Milara

et al. 2019

J Oncol Pharm Pract

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Introduction Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. Case report We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. Management and outcome The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions were needed. She achieved a good pathologic response and completed one-year adjuvant trastuzumab without incidences. Discussion Although the role of HER2 and trastuzumab in oxidative stress is not yet completely understood, we suggest that trastuzumab may be a suitable agent for treatment in patients with HER2-enriched breast cancer in a non-oxidative chemotherapy scheme, with acceptable responses and no triggering hemolytic crisis.

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“…Increased production or insufficient elimination of reactive oxygen radicals due to inhibition of HER-2 receptors was shown to cause cardiomyocyte death [27]. Dirican et al reported increased level of reactive oxygen radicals and decreased level of antioxidant enzymes 1 day after the initiation of adjuvant trastuzumab therapy, and this finding was associated with the decrease in LVEF [28]. Based on this finding, increased level of free oxygen radicals after trastuzumab therapy was considered to cause impairment of longitudinal mechanical function of the left ventricle in the early period.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional Strain Echocardiography

et al. 2015

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Aim: Trastuzumab, a chemotherapeutic agent used in the treatment of breast cancer. has been shown to induce subclinical left ventricular (LV) dysfunction during a three to six month period as evidenced by strain echocardiographic examination without any change occurring in the ejection fraction of LV. The present study evaluated the presence of subclinical LV dysfunction using strain echocardiography 1 day and 7 days after the initiation of trastuzumab therapy. Material and methods:The patients with breast cancer receiving adjuvant trastuzumab therapy underwent 2-dimensional, tissue Doppler, and strain echocardiographic examination at baseline and 1 day and 7 days after therapy. LV global longitudinal strain (GLS), global circumferential strain (GCS) values, and other echocardiographic parameters were calculated. Results: A total of 40 females, mean age 50±10 years, were evaluated. Of these patients, 97% received anthracycline and 73% received radiotherapy before the initiation of trastuzumab therapy. No change was observed in any of the echocardiographic parameters 1 day after the initiation of trastuzumab therapy (p>0.05). The LV ejection fraction, tissue Doppler parameters, and GCS values did not show any changes 7 days after the initiation of therapy, whereas significant decreases were observed in GLS value (19.2±4.0% vs. 17.2±3.4, p=0.001) and systolic annular velocity of the lateral LV wall (S' velocity) (10.5±3.2 vs. 8.6±2.2, p=0.002). Conclusion: Trastuzumab therapy is associated with subclinical LV dysfunction as early as 7 days after initiation of the therapy as evidenced by the decreases in GLS value of LV and systolic annular velocity of the lateral LV wall.

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Acute Cardiotoxic Effects of Adjuvant Trastuzumab Treatment and its Relation to Oxidative Stress

Cited by 8 publications

References 6 publications

Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab

Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab

Safe neoadjuvant trastuzumab-based treatment in HER2 + inflammatory early breast cancer in a glucose 6-phosphate dehydrogenase-deficient postmenopausal woman: A case report and review of the literature

Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional Strain Echocardiography

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