The Role of Tumor Microenvironment in Breast Cancer Progression and Treatment Resistance

Abstract

The tumour microenvironment (TME) is pivotal in the progression, metastasis, and therapeutic resistance of breast cancer. The tumour microenvironment, consisting of immune cells, stromal fibroblasts, blood vessels, extracellular matrix, and signalling chemicals, dynamically interacts with cancer cells to influence their activity. Breast tumours develop in an immunosuppressive and pro-inflammatory milieu that promotes immune evasion, angiogenesis, and resistance to treatments, particularly chemotherapy, endocrine therapy, and immunotherapy. This study investigates the intricate cellular and molecular connections within the tumour microenvironment and their roles in breast cancer heterogeneity and clinical outcomes. Data were retrospectively gathered from 2021 to 2024 at the Republican Specialised Scientific and Practical Medical Centre of Oncology and Radiology in Uzbekistan, encompassing 104 patients with histologically proven breast cancer. Patterns of immune infiltration, expression of stromal markers (including α-SMA and FAP), and cytokine profiles were examined in relation to tumour subtype, stage, and therapy response. The results indicate that tumours exhibiting high tumor-associated macrophage (TAM) density, enhanced fibroblast activation protein (FAP) expression, and raised TGF-β levels correlate with unfavourable treatment response and earlier recurrence. The research underscores the necessity of incorporating TME-targeted strategies into conventional breast cancer regimens, especially in underdeveloped nations such as Uzbekistan, where molecular profiling is constrained. Improving infrastructure for immunohistochemistry, cytokine assays, and stromal assessment may enhance therapy outcomes by identifying patients who are likely to benefit from combination methods that mitigate the suppressive effects of the microenvironment.