Metastatic Triple Negative Breast Cancer: Navigating a Rapidly Evolving Therapeutic Landscape.

Abstract

Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor, and HER2 expression, and carries a disproportionate burden of breast cancer-related mortality due to its aggressive biology and historically limited therapeutic options. The treatment landscape of metastatic TNBC has undergone a fundamental transformation over the past decade, driven by immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and the identification of actionable genomic alterations. This review provides a comprehensive, clinically oriented appraisal of the current and emerging therapeutic landscape of metastatic TNBC, encompassing its molecular underpinnings and tumour microenvironment biology. We critically evaluate the evolving roles of immune checkpoint inhibition, ADCs, PARP inhibitors, and novel targeted approaches, discuss mechanisms of resistance and biomarker limitations, and propose a framework for rational, biomarker-guided treatment selection and sequencing to support evidence-based clinical decision-making in this rapidly evolving field.