Triple negative breast Cancer classification from morphology to genomics

Abstract

Triple negative breast cancers (TNBC) comprise of a heterogenous group of tumors with an incidence of 12.3 to 13% in western populations, around 31% of all breast cancers in India (Criscitiello, Azim, Schouten, Linn, & Sotiriou, 2012). Clinically, TNBCs are associated with a younger age at presentation, higher grade at presentation, poor prognosis, and outcomes. Histologically, TNBCs were termed as basal cancers due to morphological overlap but recent publications have isolated distinct molecular markers (EGFR (epidermal growth factor receptor), HMWCK (high molecular weight cytokeratin)) which in delineating the two entities. The tumors were considered to be BRCA 1 positive, morphology showed dense which helps in delineating lymphocytic infiltrate with syncytial pattern, also termed as medullary carcinomas in the past and reclassified by WHO as infiltrating ductal carcinoma (IDC) with medullary features which are now past. They were reclassified as tumor infiltrating lymphocytes rich IDC Not otherwise specified). With the advent of next generation sequencing (NGS), genomic profiling of TNBC showed several pathways and genes involved in primary and metastatic TNBC. Lehman and Jiang separately subcategorized TNBC into molecular subtypes based on genomic profiling and also predicted therapeutic approach to these tumors. Immunotherapeutic agents became a boon with an advent of prediction of receptors on inflammatory cells in tumor microenvironment, have become a boon of tumor mutational burden and PDL1 immune check points receptors scoring. Various trials with conjunction of chemotherapeutic drugs and immunotherapy led to progression free survival in TNBC patients. Mutational signatures-based subtyping has gained prominence recently because of its role in disease prediction and prognostication. (Am J Transl Med 2021. 5 (3):138- 146).