Investigating the Link between Collagen Deposition Patterns in the TME and Indian Triple-Negative Breast Cancer Patient Outcomes

Abstract

Triple-Negative Breast Cancers (TNBCs) are characterised by the absence of hormone receptors’ expression and disproportionately burden the Indian population. Since TNBCs do not have available targets for treatment, it makes them an aggressive subset, with an unpredictable response to systemic therapy, showing higher rates of recurrence and lower overall survival, posing a significant challenge to clinical management. Therefore, there is a need to understand the factors that govern the response and treatment outcomes. Recently, the Extracellular Matrix (ECM) and its associated components have emerged as key determinants of breast cancer progression, affecting cellular behaviour, invasion and metastasis. The ECM, a complex dynamic entity, undergoes remodelling through intricate molecular interactions. These alterations are heavily context-dependent and can lead to an increase in the disease’s aggressiveness depending on what point in time they occur. Collagen is a crucial component of the ECM and plays an integral role in determining the mechanical properties of the tissue. With associated enzymes and other proteins, collagen alters matrix stiffness, alignment and density, substantially impacting tumour behaviour. The referred studies suggest that collagen-rich microenvironments correlate with aggressive tumour behaviour. With a cohort of 139 TNBC patient samples and associated clinical and follow-up data, we analyse collagen deposition in TNBC patient samples by trichrome staining to understand its association with clinical features of the tumour at presentation, treatment response and survival outcomes. By examining patient-derived tissues across pathological stages and correlating collagen deposition patterns with clinical data, our study seeks to unravel the prognostic value of ECM alterations.