CAR-T cell therapy in breast cancer management: expanding horizon and overcoming challenges beyond hematologic cancers.

Breast cancer (BC) remains one of the most prevalent and challenging cancers to treat, with current therapeutic approaches often limited by treatment resistance and adverse side effects. Chimeric Antigen Receptor T (CAR-T) cell therapy, a form of immunotherapy that re-engineers patients’ T-cells to target cancer cells, has shown substantial efficacy in hematologic malignancies and is now being explored for application in solid tumors, including BC. This review provides an in-depth overview of CAR-T cell therapy’s mechanism, design, and development, focusing on the unique challenges presented by the solid tumor environment of BC. Specifically, we discuss the critical components of CAR-T design, including antigen selection (e.g., HER2, MUC1, and EGFR), CAR structure optimisation with intracellular signalling domains, and genetic engineering techniques like CRISPR and TALENs. The review also addresses manufacturing hurdles, such as large-scale production and quality control, and highlights preclinical safety and efficacy testing models. Current clinical data on CAR-T therapy in BC, including outcomes from various subtypes and clinical trials, are reviewed, along with emerging investigational therapies. Despite its promise, CAR-T therapy in BC faces significant barriers, such as antigen heterogeneity, tumor microenvironment challenges, and safety concerns like cytokine release syndrome. Advances in next-generation CARs, combination therapies, and tumor microenvironment-modifying strategies are examined as innovative approaches to these challenges. Finally, the review explores future directions, including personalized CAR-T therapy, new target discovery, and biomarker-guided patient selection, emphasizing CAR-T potential of CAR T-therapy in reshaping breast cancer treatment. Through a comprehensive analysis, this article aims to provide insights into the current status, challenges, and future promise of CAR-T cell therapy as a transformative approach to BC management.