Impact of Nutritional Supplements and Antioxidants in the Treatment of Breast Cancer: A Systematic Review

Background/Objectives: Dietary antioxidants are frequently utilized by breast cancer (BC) patients to mitigate treatment-related toxicities and enhance quality of life. However, their clinical efficacy remains highly controversial due to conflicting epidemiological and clinical data. This review aims to critically evaluate the molecular mechanisms, clinical outcomes, and translational challenges of antioxidant supplementation in BC management. Methods: A comprehensive evaluation of current literature—encompassing observational cohorts, randomized controlled trials, and mechanistic in vitro/in vivo models—was conducted. The analysis focused on the pharmacological interactions of diverse bioactive compounds (polyphenols, vitamins, carotenoids) with BC progression and standard antineoplastic regimens. Results: Current evidence demonstrates a paradoxical, double-edged role of antioxidants in oncology. While specific interventions (e.g., Coenzyme Q10, melatonin) effectively ameliorate treatment-induced toxicities without compromising therapeutic efficacy, the concurrent administration of antioxidants during cytotoxic chemotherapy can inadvertently neutralize essential reactive oxygen species (ROS), correlating with increased disease recurrence and mortality. Furthermore, clinical translation is severely hindered by the intrinsic hydrophobicity of natural compounds, the lack of whole-food matrix standardization, and dose-dependent hepatotoxicity. Emerging targeted delivery systems, such as lipid nanoformulations, show significant potential in overcoming these pharmacokinetic barriers. Conclusions: The therapeutic viability of antioxidant supplementation in BC is not universal; it is heavily dictated by intrinsic tumor biology, specific treatment modalities, and chronopharmacology. These findings underscore a critical biological imperative to transition from generalized dietary guidelines toward a rigorous paradigm of precision nutritional oncology, strictly avoiding concurrent antioxidant supplementation during active oxidative therapies.