Blood transfusion mediated tumor microenvironment remodeling in breast cancer

Abstract

Blood transfusions play a critical role in breast cancer management, particularly in addressing perioperative blood loss and chemotherapy-induced anemia. However, emerging evidence suggests that transfusions may adversely affect oncologic outcomes by inducing transfusion-related immunomodulation (TRIM) and altering the tumor microenvironment (TME). TRIM suppresses cytotoxic immune responses, potentially facilitating tumor progression—especially in aggressive subtypes such as triple-negative breast cancer (TNBC) and HER2-positive cancers. Additionally, transfusions can paradoxically exacerbate tumor hypoxia by increasing blood viscosity and impairing microvascular perfusion, thereby reducing the effectiveness of chemotherapy, radiotherapy, and immunotherapy. This review examines the dual role of blood transfusions in breast cancer, emphasizing both their clinical benefits and potential risks. We analyze their impact on treatment resistance and tumor progression and discuss strategies to mitigate associated risks, including leukoreduction, erythropoiesis-stimulating agents (ESAs), intravenous iron supplementation, and blood conservation techniques. Furthermore, we highlight the importance of personalized transfusion approaches guided by tumor subtype, immune status, and relevant biomarkers such as tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and circulating tumor DNA (ctDNA). Future research should focus on optimizing transfusion timing, implementing biomarker-driven protocols, and developing immune-modulating interventions to counteract TRIM. A personalized, evidence-based transfusion strategy may ultimately enhance treatment efficacy and improve long-term outcomes in breast cancer care.