Evolving Paradigms in Breast Cancer Treatment: Targeted, Gene, and Nanomedicine Strategies for Precision Care

Abstract

Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer-related deaths worldwide. Despite significant advances in therapy, tumour heterogeneity, drug resistance, and treatment-associated toxicity remain major challenges in clinical management. The shift from conventional systemic therapies to targeted and precision medicine approaches based on biomarkers has revolutionized the breast cancer treatment landscape. This narrative review was conducted using broad search terms across PubMed, Scopus, Web of Science, and Google Scholar, covering publications from 2013 to 2025. The search strategy included terms such as breast cancer, endocrine therapy, HER2- targeted therapy, gene therapy, immunotherapy, nanomedicine, pharmacogenomics, predictive biomarkers, and precision medicine. Phase I–III clinical trials, translational studies, and high-impact peer-reviewed publications were included. Emphasis was placed on the quality and relevance of the evidence rather than on comprehensive inclusion of all available studies. The introduction of novel endocrine therapies and HER2-targeted treatments has significantly improved survival outcomes for patients with hormone receptor-positive and HER2-positive breast cancer. Although treatment benefits vary among patients, the therapeutic landscape has expanded considerably with the development of PARP inhibitors, trastuzumab-based antibody–drug conjugates (T-DXd), and CDK4/6 inhibitors. Emerging approaches, including gene therapy and immunotherapy, have also shown promise, although clinical evidence continues to evolve. Meanwhile, molecular subtyping based on predictive biomarkers has become increasingly important, with markers such as ESR1 and PIK3CA mutations, BRCA mutations, HER2-low status, and PD-L1 expression being used to guide treatment selection. This approach supports more personalized therapeutic decisions, moving beyond the traditional one-size-fits-all model. Despite substantial progress in improving therapeutic outcomes, several challenges continue to limit clinical effectiveness, including acquired resistance, tumour heterogeneity, the lack of standardized biomarkers, and economic constraints. Addressing these limitations will require the integration of multi-omics profiling, real-time molecular monitoring, and adaptive precision medicine algorithms to optimize treatment sequencing and improve patient outcomes. Breast cancer management has increasingly shifted toward precision oncology, driven by advances in molecular diagnostics and targeted therapeutic interventions. The continued development of predictive biomarkers, together with ongoing research into combination therapies and translational studies, is expected to play a critical role in determining the future success of personalized medicine approaches.