Role of Carbonic Anhydrase IX Expression in Triple-negative Breast Cancer

This retrospective analysis includes 50 patients diagnosed with TNBC at the Gujarat Cancer and Research Institute (GCRI).Clinical parameters, including age, menopausal status, histopathological details, disease staging, and treatment history, were obtained from introduction Triple-negative breast cancer (TNBC) is considered an aggressive breast cancer variant, associated with elevated 5-year mortality owing to the absence of established therapeutic markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). 1 Carbonic anhydrase IX (CA IX) is a tumor-associated cell surface glycoprotein whose expression is mainly regulated through activation of the hypoxia-inducible factor 1 alpha (HIF1) transcription factor under hypoxic conditions. 2 CA IX leads to extracellular acidification through the reversible hydration of CO 2 into HCO 3 -and protons, thereby leading to a microenvironment that promotes tumor cell stemness, metastasis, treatment resistance, and immune evasion. 3,4 CA IX also promotes matrix degradation, epithelial-mesenchymal transition, invasion, altered adhesion, inflammation, and angiogenesis.It is highly expressed in tumors compared to normal tissues. 5,6TNBC is often highly proliferative, outgrowing its blood supply, leading to severe hypoxia. 7Thus, CA IX overexpression within invasive mammary tumors shows strong correlation with poor outcomes and reduced diseasefree survival (DFS), indicating its association with aggressive tumor behavior. 8Accordingly, the study investigated the clinical impact of CA IX expression in TNBC and its relationship with key clinicopathological parameters and disease status.