Key result
Antioxidants show preclinical promise in mitigating trastuzumab-induced cardiotoxicity, pending clinical validation.
Why the study?
Trastuzumab cardiotoxicity often requires stopping therapy, and oxidative stress plays a fundamental role in its poorly understood pathophysiology.
Does antioxidant adjuvant therapy prevent trastuzumab-induced cardiotoxicity in patients with HER2-positive breast cancer?
Does antioxidant adjuvant therapy prevent trastuzumab-induced cardiotoxicity in patients with HER2-positive breast cancer?
Antioxidants represent a biologically plausible strategy for mitigating trastuzumab-induced cardiotoxicity by targeting oxidative stress, highlighting an area needing prospective clinical trials.
Antioxidants lack evidence for clinical use in trastuzumab therapy; leaves open whether preclinical signals translate to reduced cardiotoxicity in trials.
Breast cancer is the most frequent malignant neoplastic disease in women, with an estimated 2.3 million cases in 2020 worldwide. Its treatment depends on characteristics of the patient and the tumor. In the latter, characteristics include cell type and morphology, anatomical location, and immunophenotype. Concerning this latter aspect, the overexpression of the HER2 receptor, expressed in 15-25% of tumors, is associated with greater aggressiveness and worse prognosis. In recent times some monoclonal antibodies have been developed in order to target HER2 receptor overexpression. Trastuzumab is part of the monoclonal antibodies used as targeted therapy against HER2 receptor, whose major problem is its cardiac safety profile, where it has been associated with cardiotoxicity. The appearance of cardiotoxicity is an indication to stop therapy. Although the pathophysiological mechanism is poorly known, evidence indicates that oxidative stress plays a fundamental role causing DNA damage, increased cytosolic and mitochondrial ROS production, changes in mitochondrial membrane potential, intracellular calcium dysregulation, and the consequent cell death through different pathways. The aim of this review was to explore the use of antioxidants as adjuvant therapy to trastuzumab to prevent its cardiac toxicity, thus leading to ameliorate its safety profile in its administration.
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Méndez-Valdés et al. (2023) conducted a review in HER2-positive breast cancer with risk of trastuzumab-induced cardiotoxicity. Antioxidants (as adjuvant therapy) was evaluated. Antioxidant supplementation shows potential in preclinical models to mitigate trastuzumab-induced oxidative stress and cardiotoxicity, though clinical trials are needed to confirm safety and efficacy.
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