Copper and Zinc Complexes as Anti‐Breast Cancer Agents: Their Role, Mechanisms, and Biological Activities

ABSTRACT Breast cancer remains one of the leading causes of cancer‐related mortality worldwide, particularly in aggressive and treatment‐resistant subtypes such as triple‐negative breast cancer (TNBC). Growing limitations associated with conventional chemotherapy, including systemic toxicity, drug resistance, and poor selectivity, have stimulated interest in metal‐based therapeutics. This review critically evaluates recent advances in copper‐ and zinc‐based anticancer systems, including coordination complexes, Schiff bases, thiosemicarbazones, phenanthroline derivatives, pyridine–thiazole ligands, metal–organic frameworks, and zinc oxide nanoparticles. Copper complexes generally exhibit potent anticancer activity through redox‐mediated mechanisms involving the generation of reactive oxygen species (ROS), DNA damage, mitochondrial dysfunction, and inhibition of angiogenesis. In contrast, zinc‐based systems are largely redox‐silent and exert their effects through biomolecular interactions, enzyme regulation, induction of apoptosis, and improved selectivity for cancer cells. Emphasis is placed on structure–activity relationships, mechanistic pathways, breast cancer stem cell targeting, and nanotechnology‐assisted delivery strategies. A comparative analysis highlights the distinct advantages and limitations of Cu‐ and Zn‐based systems in breast cancer therapy. Despite promising preclinical outcomes, challenges related to toxicity, pharmacokinetics, and clinical translation remain significant. The review identifies current research gaps and discusses future directions for the rational design of safer and more effective metal‐based therapeutics for breast cancer management.