Risk factors associated with trastuzumab-induced cardiotoxicity in patients with human epidermal growth factor receptor 2-positive breast cancer

Abdel-Razaq, Wesam; Alzahrani, Mohammed; Yami, Majed S. Al; Almugibl, Faisal; Almotham, Mohammed; Alregaibah, Razan

doi:10.4103/jpbs.jpbs_276_18

Cited by 10 publications

(11 citation statements)

References 36 publications

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“…Furthermore, 75% of the patients in Hamed et al's study (32) were young. In complete accordance with our study are the results of Abdel-Razaq et al (33), who reported 21.9% TIC in 146 patients from two local hospitals in a study spanning almost 3 years. ------------------------------------------------------------------ A higher BMI is associated with an increase in risk-related cardiotoxicity in breast cancer patients (34).…”

Section: Discussionsupporting

confidence: 93%

Incidence of trastuzumab‑induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center

et al. 2022

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The effect of BMI as a risk factor in trastuzumabinduced cardiotoxicity in Saudi patients with HER2-neu positive breast cancer treated with trastuzumab and anthracyclines is not fully understood. The present study retrospectively evaluated the overall incidence of cardiotoxicity and the effect of BMI as a risk factor for cardiotoxicity. A retrospective study performed between 2011 and 2015 of patients with Her2-neu positive early breast cancer who were treated with either a combination of trastuzumab and anthracycline or a combination of trastuzumab with non-anthracycline or hormonal treatment in the adjuvant settings was carried out. The incidence of cardiotoxicity and the effect of BMI, hypertension and diabetes mellitus as risk factors for cardiotoxicity were assessed. Cardiotoxicity was measured using a drop in the ejection fraction of >10 percentage points to a left ventricular ejection fraction of <50%. The present cohort included 105 patients diagnosed with stage I and II breast cancer. The mean age of the present cohort was 47.5±1.0 years (range, 25-76 years), the mean height was 153.9±14.1 cm (range, 126-170 cm), the mean body weight was 75.7±15.6 kg (range, 40-143 kg) and the mean BMI was 31.3±5.8 (range, 18-49). Cardiotoxicity was detected in 21.9% of the cohort. The BMI was calculated for 81 patients who were treated with a combination of trastuzumab and anthracycline. Cardiotoxicity was detected in 3 out of 9 patients with a BMI <25, in 9 out of 23 patients with a BMI between 25 and 29, and in 6 patients with a BMI >30. There was a significant association between cardiotoxicity and BMI (P= 0.03). No significant association between age, hypertension and diabetes and cardiotoxicity was identified. In conclusion, compared with global cohorts, the present results revealed a higher incidence of cardiotoxicity among Saudi patients with HER2-neu positive early breast cancer treated with trastuzumab combinations in adjuvant settings. Increased BMI was significantly associated with cardiotoxicity.

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Section: Discussionsupporting

confidence: 93%

Incidence of trastuzumab‑induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center

et al. 2022

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“…However, the effectiveness of conventional cytotoxic drugs is largely based on the generation of ROS and consequently on the increase of oxidative stress that exceeds the reduction capacity of cancerous tissue, resulting in apoptotic cell death [ 73 ], and most of the adverse effects emanating from chemotherapy result from excess ROS production in healthy tissues, such as anthracycline-mediated cardiotoxicity, and nephrotoxicity triggered by platinum compounds [ 74 , 75 ] which are mainly based on the interaction of OH • with target tissue DNA [ 76 , 77 ]. TZM has been reported to potentiate cardiomyocyte toxicity through a “dual-hit” mechanism, which includes alterations in antiapoptotic signalling pathways in cardiomyocytes, inhibition of the neuregulin-1 survival signaling pathway, and angiotensin II-induced activation of NADPH oxidase, with the ability to further increase reactive oxygen species production, ultimately resulting in dilated cardiomyopathy [ 78 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

African Vegetables (Clerodendrum volubile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats

Olorundare

Adeneye

Akinsola

et al. 2020

Oxidative Medicine and Cellular Longevity

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Trastuzumab (TZM) is a humanized monoclonal antibody that has been approved for the clinical management of HER2-positive metastatic breast and gastric cancers but its use is limited by its cumulative dose and off-target cardiotoxicity. Unfortunately, till date, there is no approved antidote to this off-target toxicity. Therefore, an acute study was designed at investigating the protective potential and mechanism(s) of CVE and IGE in TZM-induced cardiotoxicity utilizing cardiac enzyme and oxidative stress markers and histopathological endpoints. 400 mg/kg/day CVE and IGE dissolved in 5% DMSO in sterile water were investigated in Wistar rats injected with 2.25 mg/kg/day/i.p. route of TZM for 7 days, using serum cTnI and LDH, complete lipid profile, cardiac tissue oxidative stress markers assays, and histopathological examination of TZM-intoxicated heart tissue. Results showed that 400 mg/kg/day CVE and IGE profoundly attenuated increases in the serum cTnI and LDH levels but caused no significant alterations in the serum lipids and weight gain pattern in the treated rats. CVE and IGE profoundly attenuated alterations in the cardiac tissue oxidative stress markers’ activities while improving TZM-associated cardiac histological lesions. These results suggest that CVE and IGE could be mediating its cardioprotection via antioxidant, free radical scavenging, and antithrombotic mechanisms, thus, highlighting the therapeutic potentials of CVE and IGE in the management of TZM-mediated cardiotoxicity.

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“…Another report had also earlier suggested cardiotoxicity association due to treatment with the trastuzumab and pertuzumab combination [26]. Recently, Abdel-Razaq et al [27] reported that 90% of HER2positive breast cancer patients showed trastuzumab-induced cardiotoxicity in Saudi Arabia. Similar to our observations, Abulkhair et al…”

Section: Discussionmentioning

confidence: 92%

Cardiotoxicity among Patients Using Pertuzumab, Trastuzumab and Taxane with HER2-Positive Early-Stage Breast Cancer: A Single-Centre Experience

Algarni

Alfi

Turkistani

et al. 2021

JPRI

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Aim: In this study, we aimed to investigate the incidence rate, risk factors, and mortality rates in patients with early-stage breast cancer using anti-HER2 (Human epidermal growth factor receptor-2) treatment. Patients and Methods: A total of 106 patients diagnosed with human epidermal growth factor 2 (HER2)-positive early-stage breast cancer and receiving anti-HER2 treatment at King Abdulaziz Medical City (KAMC) from 2015 to 2019 were included in the analysis to assess the incidence of cardiotoxicity was collected as a retrospective study. Univariate and multivariate analyses as well as multiple exact logistic regression analysis were conducted to understand the relationships between the left ventricular ejection fraction (LVEF) and treatment combinations and comorbidities Results: The LVEF measurements using an echocardiography method at the baseline (before any treatment) and during the anti-HER2 therapy were assessed. The results suggest that the higher the drug combination, the higher the odds ratio for the declined ejection fraction (EF) patient group. Further, patients treated with the pertuzumab and trastuzumab combination were four times more likely to have a decline in their EF than those who did not use the pertuzumab and trastuzumab drug combination (OR 4.28, 95% CI [1.68–10.91]). Conclusion: This study demonstrated that the drug combination considered here is associated with reduced LVEF and, similarly, comorbidities were also related to EF. However, a larger study in a global patient population will confirm the present observations.

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Risk factors associated with trastuzumab-induced cardiotoxicity in patients with human epidermal growth factor receptor 2-positive breast cancer

Cited by 10 publications

References 36 publications

Incidence of trastuzumab‑induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center

Incidence of trastuzumab‑induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center

African Vegetables (Clerodendrum volubile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats

Cardiotoxicity among Patients Using Pertuzumab, Trastuzumab and Taxane with HER2-Positive Early-Stage Breast Cancer: A Single-Centre Experience

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