Breast cancer (BC) is the most common malignancy in women worldwide, and it is a molecularly diverse disease. Heterogeneity can be observed in a wide range of cell types with varying morphologies and behaviors. Molecular classifications are broadly used in clinical diagnosis, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and breast cancer gene (BRCA) mutations, as indicators of tumor heterogeneity. Treatment strategies differ according to the molecular subtype. Besides the traditional treatments, such as hormone (endocrine) therapy, radiotherapy, and chemotherapy, innovative approaches have accelerated BC treatments, which contain targeted therapies and immunotherapy. Among them, monoclonal antibodies, small-molecule inhibitors and antibody–drug conjugates, and targeted delivery systems are promising armamentarium for breast cancer, while checkpoint inhibitors, CAR T cell therapy, cancer vaccines, and tumor-microenvironment-targeted therapy provide a more comprehensive understanding of breast cancer and could assist in developing new therapeutic strategies.

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome‐based nanocomplexes containing pro‐apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross‐linked nanohydrogels (Herceptin‐HA) to fabricate a HER2/CD44‐targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin‐HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2‐positive SKBR‐3, triple‐negative MDA‐MB‐231, and HER2‐negative drug‐resistant MCF‐7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2‐positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.