Harnessing CAR T-Cells Against Breast Cancer: A Comprehensive Review

Breast cancer represents a highly heterogeneous malignancy encompassing multiple molecular subtypes, each with distinct therapeutic responses and clinical outcomes. Conventional treatment strategies—including surgery, chemotherapy, radiotherapy, endocrine, and targeted therapies—have improved survival rates but continue to face major limitations due to tumor relapse, metastasis, and therapy-induced resistance. In recent years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative modality in cancer immunotherapy, offering targeted and durable antitumor activity. While its efficacy in hematological malignancies is well established, translation to solid tumors such as breast cancer remains hindered by a complex interplay of tumor-intrinsic and micro environmental barriers. This review delineates the mechanistic underpinnings of CAR T-cell function and highlights the multifaceted challenges posed by solid tumors, including antigen heterogeneity, an immunosuppressive tumor microenvironment, inadequate trafficking and infiltration, limited T-cell persistence, and safety-related cytotoxicities. Finally, emerging strategies and innovations aimed at overcoming these barriers are discussed, highlighting the potential and future direction of CAR T-cell therapy in breast cancer management. Collectively, this review underscores the translational potential of CAR T-cell therapy for breast cancer and outlines the rational strategies required to enhance its clinical applicability and therapeutic efficacy in solid tumor settings.