TMSS Medical College Journal

Breast cancer is not a single disease. It is a biologically heterogeneous collection of malignancies, each with its own molecular fingerprint, natural history, and therapeutic vulnerability. For decades, the clinical management of breast cancer rested on a triad of morphology, staging, and the immunohistochemical (IHC) expression of three cardinal biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), supplemented by the proliferation index Ki-67.¹ This IHC-based surrogate classification formalised by the St. Gallen International Consensus has undeniably transformed breast oncology, stratifying patients into five clinically actionable subtypes and guiding systemic therapy decisions with meaningful prognostic discrimination. Yet the limitations of this approach have grown increasingly apparent as precision oncology matures: IHC surrogates achieve molecular concordance of only 80–85% with gene expression profiling, are subject to inter observer variability, and critically fail to capture the dynamic intra-tumoral genomic complexity that underlies treatment resistance.³ The clinical imperative to move beyond IHC is now well evidenced. Multigene expression assays Oncotype DX, MammaPrint, Prosigna, and Endo Predict have demonstrated robust prospective validation as tools for chemotherapy decision-making in hormone receptor-positive, HER2 negative early breast cancer, with the TAILORx and MINDACT trials establishing their capacity to spare a substantial proportion of patients from unnecessary cytotoxic therapy.⁴,⁵ In the HER2 positive space, the DESTINY