A new Research Topic published in Frontiers in Oncology argues that this picture is incomplete. Its six articles, gathered under the title “Roles of metabolism, immunity, and microbiome in the pathophysiology of the breast cancer microenvironment,” examine how metabolic processes, inflammatory signals, immune responses and even the bacteria living in the gut may influence how breast cancer develops, progresses and responds to treatment. The editorial accompanying the collection, written by Saori Furuta of Case Western Reserve University School of Medicine, emphasizes that the overall health and metabolic condition of patients may also shape disease outcomes, a dimension that is often absent from purely cell-centered models of cancer.
The collection opens with a study that brings the whole body back into the frame. The appeal of this approach lies in its practicality: the indicators the team examined can be measured using common clinical tests that patients already undergo routinely. Their findings suggest that metabolic and inflammatory conditions in the body may be related to breast cancer risk. The editorial stresses that such associations highlight the importance of considering not only cancer cells but also the overall physiological condition of patients when studying the disease, rather than treating the tumor as an isolated entity.
Inside the tumor itself, metabolism is proving to be more than a simple supply line of energy. A second contribution, also led by Chen and colleagues, examines lactylation, a process in which a lactyl group is added to a protein, potentially changing its function. Lactate was long regarded as little more than a waste product of glucose metabolism, but recent research suggests it may also influence gene expression and cellular activity through this chemical modification. Using single-cell and other molecular analyses, the study explores how metabolic changes may affect the different cell populations within the tumor microenvironment. Notably, the authors report that lactylation-related features may be useful for predicting clinical outcomes in breast cancer, raising the possibility that a metabolic byproduct could carry prognostic information encoded directly into the proteome of tumor tissue.
Where cells sit within a tumor matters as much as what they are doing. In a review article, He and colleagues discuss what they call the tripartite axis of immune-metabolic-spatial crosstalk in breast cancer. Different regions of a tumor may have different levels of oxygen and nutrients, and cancer cells and immune cells may compete for these resources. The distribution of immune cells and surrounding stromal cells also affects how they interact. Together, the authors argue, these factors can influence the ability of immune cells to attack tumors and may contribute to resistance to cancer treatment.
Hormones that regulate metabolism provide another possible bridge between the body’s condition and the behavior of breast cancer. A review by Chen and colleagues focuses on fibroblast growth factor 21, or FGF21, a hormone involved in regulating glucose and lipid metabolism. Its role in breast cancer is not yet fully understood, but current evidence suggests that FGF21 signaling may influence cancer-related biological processes. The editorial is careful on this point: further research is needed to determine whether FGF21 could serve as a biomarker or therapeutic target, and it remains important to establish whether its effects differ among breast cancer subtypes and among patients with different metabolic conditions. The review thus frames FGF21 as a promising but unresolved question rather than a settled mechanism.
The collection also looks beyond the tumor to the gut. The gut microbiome can affect inflammation, immune responses and the production of metabolites that influence cellular functions, and these changes may in turn affect tumor growth and response to treatment. The editorial notes an important caveat: further studies are needed to determine whether changes in the gut microbiome directly contribute to breast cancer progression or are merely associated with other disease-related factors. Distinguishing cause from correlation is a recurring theme throughout the collection, and the microbiome work is no exception.
Metabolic research in this collection is not confined to tumor control. Jiang and colleagues turn to cancer-related fatigue, a common problem that can greatly affect patients' daily activities and quality of life. Using metabolomics, an approach that measures the small molecules involved in metabolism, the authors explore metabolic changes associated with breast cancer-related fatigue and discuss possible approaches to managing the condition, including traditional Chinese medicine interventions. The editorial suggests that understanding these metabolic changes could help researchers identify biomarkers and develop better approaches to symptom management, demonstrating how metabolic research may benefit patients beyond improving tumor control.
Taken together, the six articles address systemic inflammation and nutrition, lactylation in the tumor microenvironment, interactions between metabolism and immunity, hormonal regulation, the gut microbiome and cancer-related fatigue. The editorial argues that they share a common message: breast cancer is influenced not only by cancer cells but also by their surrounding environment and the metabolic condition of the patient. Metabolism, in this view, is not limited to cancer cells; it also affects immune cells, stromal cells and other tissues throughout the body.
The editorial is equally candid about what the collection does not yet establish. Many findings from clinical observations, metabolomics and single-cell analyses show associations, but additional experiments are needed to determine whether these factors directly affect breast cancer development or progression. Future studies should also examine whether the findings apply across different breast cancer subtypes, disease stages and patient populations. The editorial suggests that combining molecular analyses, immune profiling, microbiome research and clinical data may help researchers better understand how these factors interact, and could distinguish metabolic changes that contribute to disease progression from changes that result from the cancer itself or its treatment. That distinction is critical, because a metabolic signature observed in a tumor sample may be either a driver of the disease or a downstream consequence of it.
By improving understanding of how tumor metabolism, immune behavior, spatial organization, hormonal signals and the microbiome interact, the editorial argues, future research may identify new biomarkers, improve cancer treatments and support better management of treatment-related symptoms. These advances, it concludes, could ultimately improve both treatment outcomes and quality of life for patients with breast cancer. The collection is a snapshot of a field in transition, one that is moving from the cancer cell in isolation toward the patient as a whole metabolic and immunological system, and it makes clear that much of the most consequential work still lies ahead.
Subject of Research: How metabolism, immunity and the microbiome influence the breast cancer microenvironment
Article Title: Editorial: Roles of metabolism, immunity, and microbiome in the pathophysiology of the breast cancer microenvironment
Article References: Furuta, S. (2026). Editorial: Roles of metabolism, immunity, and microbiome in the pathophysiology of the breast cancer microenvironment. Frontiers in Oncology, 16, Article 2014425. https://doi.org/10.3389/fonc.2026.2014425
Image Credits: AI Generated
DOI: 10.3389/fonc.2026.2014425
Keywords: breast cancer, cancer metabolism, tumor microenvironment, tumor immunology, gut microbiome, inflammation, lactylation, FGF21, cancer-related fatigue, metabolomics, triple-negative breast cancer, therapy resistance
News Source: Nathaniel Bowman. (October 28, 2026). Metabolism, immunity and the microbiome shape the breast cancer microenvironment. Scienmag.
