Therapeutic challenges in breast cancer: Navigating the impact of oxidative stress on treatment efficacy and toxicity

Breast cancer remains one of the most prevalent and challenging malignancies worldwide, necessitating a multifaceted therapeutic approach. Although current treatments- including chemotherapy, radiotherapy, targeted therapy, and hormone therapy- have significantly improved patient outcomes, they are often associated with substantial adverse effects and therapeutic resistance. Emerging evidence underscores the critical role of oxidative stress in mediating both the efficacy and toxicity of these treatments. Reactive oxygen species (ROS), generated either endogenously or as a byproduct of anticancer therapies, contribute to cellular damage, inflammation, and impaired redox homeostasis, ultimately influencing treatment outcomes. This review systematically explores the mechanisms by which oxidative stress modulates the biological response to anthracyclines, taxanes, and ionizing radiation, and highlights its involvement in treatment-induced cardiotoxicity, neurotoxicity, fibrosis, and immune dysregulation. Additionally, we examine the role of oxidative stress in resistance to HER2-targeted and hormone-based therapies. The article further discusses combination therapy-induced synergistic toxicity and outlines current and emerging antioxidant-based strategies- ranging from natural compounds and synthetic agents to nanomedicine and gene modulation- that may mitigate oxidative damage. Understanding the complex interplay between redox biology and therapeutic response offers new opportunities for improving treatment efficacy, minimizing adverse effects, and advancing personalized interventions in breast cancer care.