Invasive Ductal Carcinoma of the Breast: Molecular Evolution, Immune Escape, and Therapeutic Implications
Abstract
- Invasive ductal carcinoma (IDC) is the most common histological form of breast cancer and is characterized by marked molecular and immunological heterogeneity. Its progression from ductal carcinoma in situ (DCIS) to invasive disease is accompanied by disruption of the myoepithelial and basement-membrane barriers, extracellular-matrix remodelling, genomic evolution and changes in the tumour microenvironment (TME). Cancer immunoediting provides a useful framework for understanding this progression through elimination, equilibrium and escape. During escape, tumour cells and associated stromal and immune populations can reduce effective antitumour immunity through altered antigen presentation, immune-checkpoint signalling, immunosuppressive cytokines, metabolic reprogramming and recruitment of regulatory immune cells. Evidence from breast tumours demonstrates reduced cytotoxic T-cell activity and changes in immune-cell composition during the transition from DCIS to IDC. Genomic alterations involving TP53, PIK3CA and GATA3 contribute to subtype-specific tumour behaviour, while emerging studies implicate metabolic regulators such as acyl-CoA thioesterase 7 (ACOT7) in IDC biology and immune contexture. PD-L1 assessment illustrates the translational challenge of converting tumour immunobiology into reliable clinical biomarkers because assay platforms, scoring systems and specimen characteristics can influence classification. Therapeutically, immune-checkpoint blockade has become clinically important in selected breast-cancer populations, particularly early-stage triple-negative disease, while antibody – drug conjugates have expanded treatment options for HER2-low advanced breast cancer. This review synthesizes the immunological and molecular mechanisms underlying IDC progression, highlights diagnostic and therapeutic implications, and identifies research priorities relevant to resource-constrained settings.