The relevance of tumor microenvironment for clinical outcomes in breast cancer

New data recently published on Cell Reports Medicine show that in breast cancer 7 distinct tumor microenvironment (TME) exist and are associated with clinical outcomes, independently of genomic subtypes.

Researchers compared in 693 breast cancer samples 15 computational methods able to estimate TME compositions. The best performing was then used to analyze a dataset of nearly 15.000 breast cancer expression profiles. Results identified 7 distinct TME types that associated with disease-free survival independently of intrinsic and genomic subtypes. Some TME features modulate chemotherapy response, relapse, and metastatic risk: for example, long-term recurrence was regulated by vascular stromal cells and the innate immune response, whereas naive B cells were uniformly depleted across all metastatic lesions. This supports the hypothesis that metastatic seeding cells may evolve to evade B cell-driven immune pressure, thus indicating opportunity for therapeutic intervention. As authors highlight, «We uncovered complex and distinct associations between specific TME cell populations and clinical endpoints, shaped by estrogen receptors status and molecular subtype. These findings have potential utility for improving tumor prognostication, predicting relapse and treatment response, and guiding the development of tailored therapeutic strategies». TME contributes to breast cancer heterogeneity and outcome but is rarely considered in clinical decision-making: these new data help to address this gap because as authors conclude «TME composition may serve as an independent biomarker for prognosis and therapy selection, complementing existing clinical and genomic markers, to better guide patient management and the development of more precise strategies to prevent relapse and metastasis».