Emerging therapeutic frontiers in breast cancer management: From nanotechnology and immunotherapy to targeted drug delivery and novel biomarkers

Breast cancer remains the most frequently diagnosed malignancy in women worldwide and continues to present substantial therapeutic challenges, including systemic toxicity, limited target specificity, drug resistance, and disease recurrence. This review examines emerging strategies addressing these challenges across the spectrum of clinical development, from established standard-of-care agents to investigational approaches. Nanotechnology-based drug delivery systems—including nanoparticles, liposomes, niosomes, nanoemulsions, phytosomes, micelles, dendrimers, and ethosomes—offer improved bioavailability and tumor selectivity, although the large majority remain preclinical. Combination regimens can outperform single-agent treatment by achieving synergistic efficacy and delaying resistance. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 and CTLA-4 axes, cancer vaccines, and adoptive cell therapy (ACT), has produced durable clinical benefit, especially in triple-negative breast cancer (TNBC). Targeted therapies—including bispecific monoclonal antibodies, antibody-drug conjugates (ADCs), and molecular inhibitors of CDK4/6, PI3K, PARP, VEGF, EGFR, and mTOR—enable precision-medicine approaches, several of which are now guideline-endorsed for defined patient subgroups. Non-invasive modalities such as photodynamic, photothermal, and sonodynamic therapy, together with gene therapy strategies using viral and non-viral vectors, represent additional, largely experimental avenues. Novel biomarkers, including gene alterations (BRCA1/2, PTEN, CHEK2, ATM), circular RNAs (circSMARCA5, circ_0044234), and microRNAs, show promise for prognostic and predictive stratification, although most require further clinical validation before routine use. Collectively, these approaches represent a transformative, subtype-informed trajectory for breast cancer management that must still reconcile preclinical promise with pharmacokinetic, manufacturing, and regulatory realities.