Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving metabolic resistance in both primary and metastatic breast cancer, and how the unique metabolic environments in metastatic sites further complicate treatment. By targeting distinct metabolic vulnerabilities at both the primary and metastatic stages, new strategies could improve the efficacy of existing therapies and provide better outcomes for breast cancer patients.

The extracellular matrix (ECM) forms a dynamic structure around cells, providing environmental cues, mechanical support, and tissue protection. It is composed of fibrous proteins, glycosaminoglycans (GAGs), proteoglycans, and glycoproteins. The molecular, physical, and mechanical properties of the ECM regulate the motility, survival, and function of immune cells. In most cancers, inflammatory cytokines and proteases—particularly matrix metalloproteinases(MMPs)—released within the immune-infiltrated inflammatory microenvironment can remodel the ECM. Cytokines such as tumor necrosis factor-α (TNF), interleukin, and transforming growth factor-beta (TGF-β) modulate the expression of various ECM molecules and promote host cell differentiation, thereby shaping a stroma conducive to tumor survival and metastasis. When ECM components become dysregulated, they act as ligands interacting with immune cell receptors, suppressing the function of specific immune cell subsets in the tumor microenvironment (TME), and activating downstream intracellular signaling pathways that are exploited by cancer cells to facilitate progression. This review systematically outlines key ECM constituents, molecular mediators of ECM remodeling, and their role in regulating immune cell behavior, including T cell exhaustion and macrophage polarization. It also elucidates the direct interactions between ECM and immune cells within inflammatory settings. Furthermore, we explore therapeutic strategies targeting ECM-mediated immunosuppression in solid tumors. This study highlights promising approaches to enhance the efficacy of cancer immunotherapy.

Breast cancer is the most prevalent malignant neoplasm worldwide, necessitating the development of novel therapeutic strategies owing to the limitations posed by conventional treatment modalities. Immunotherapy is an innovative approach that has demonstrated significant efficacy in modulating a patient's innate immune system to combat tumor cells. In the era of precision medicine, adoptive immunotherapy for breast cancer has garnered widespread attention as an emerging treatment strategy, primarily encompassing cellular therapies such as tumor-infiltrating lymphocyte therapy, chimeric antigen receptor T/natural killer/M cell therapy, T cell receptor gene–engineered T cell therapy, lymphokine-activated killer cell therapy, cytokine-induced killer cell therapy, natural killer cell therapy, and γδ T cell therapy, among others. This treatment paradigm is based on the principles of immune memory and antigen specificity, involving the collection, processing, and expansion of the patient's immune cells, followed by their reintroduction into the patient's body to activate the immune system and prevent tumor recurrence and metastasis. Currently, multiple clinical trials are assessing the feasibility, effectiveness, and safety of adoptive immunotherapy in breast cancer. However, this therapeutic approach faces challenges associated with tumor heterogeneity, immune evasion, and treatment safety. This review comprehensively summarizes the latest advancements in adoptive immunotherapy for breast cancer and discusses future research directions and prospects, offering valuable guidance and insights into breast cancer immunotherapy.

Anti-PD-1/PD-L1 treatment has achieved durable responses in TNBC patients, whereas a fraction of them showed non-sensitivity to the treatment and the mechanism is still unclear. Pre- and post-treatment plasma samples from triple negative breast cancer (TNBC) patients treated with immunotherapy were measured by tandem mass tag (TMT) mass spectrometry. Public proteome data of lung cancer and melanoma treated with immunotherapy were employed to validate the findings. Blood and tissue single-cell RNA sequencing (scRNA-seq) data of TNBC patients treated with or without immunotherapy were analyzed to identify the derivations of plasma proteins. RNA-seq data from IMvigor210 and other cancer types were used to validate plasma proteins in predicting response to immunotherapy. A random forest model constructed by FAP, LRG1, LBP and COMP could well predict the response to immunotherapy. The activation of complement cascade was observed in responders, whereas FAP and COMP showed a higher abundance in non-responders and negative correlated with the activation of complements. scRNA-seq and bulk RNA-seq analysis suggested that FAP, COMP and complements were derived from fibroblasts of tumor tissues. We constructe an effective plasma proteomic model in predicting response to immunotherapy, and find that FAP⁺ and COMP⁺ fibroblasts are potential targets for reversing immunotherapy resistance.

Breast cancer is the most widespread malignant tumor worldwide. Single-cell sequencing technology offers novel insights and methods to understand the onset, progression, and treatment of tumors. Nevertheless, there is currently an absence of a thorough and unbiased report on the comprehensive research status of single-cell sequencing in breast cancer. This study seeks to summarize and quantify the dynamics and trends of research on breast cancer single-cell sequencing by bibliometric analysis. Research articles and reviews related to breast cancer single-cell sequencing were selected from the WoSCC database. Visualization of data regarding countries, institutions, authors, references, and keywords was performed by CiteSpace and VOSviewer software. 583 articles and reviews were analyzed in this study. The quantity of publications related to breast cancer single-cell sequencing has been increasing annually. These studies originate from 302 institutions in 46 countries, with YMAX S WICHA producing the most publications and WANG Y being the most cited author. Nature Communications is the most researched journal, while Nature holds the highest number of citations. These journals predominantly cover topics in the molecular/biological/immunological fields. Moreover, an analysis of reference and keyword bursts revealed that current research trends in this area are primarily centered on "clonal evolution," "tumor microenvironment," and "immunotherapy." Breast cancer single-cell sequencing is a rapidly growing area of scientific interest. Future research requires more frequent and in-depth collaborations among countries, institutions, and authors. Furthermore, "clonal evolution," "tumor microenvironment," and "immunotherapy" are likely to become major focal points in upcoming research on breast cancer single-cell sequencing.