Targeting the Molecular Subtypes of Triple Negative Breast Cancer: Understanding the Diversity to Progress the Field

Triple negative breast cancers (TNBCs) represent 10%-20% of primary breast cancers, and despite having greater initial sensitivity to cytotoxic chemotherapy, patients with TNBCs have higher rates of distant metastasis and a poorer prognosis compared with patients with hormone receptor positive and/or human epidermal growth factor receptor 2 positive disease. TNBC has historically been treated as a single disease entity in targeted therapy trials, but advances in gene expression profiling and other molecular diagnostic techniques over the last decade have revealed considerable biologic heterogeneity within TNBCs, including subgroups with distinct, targetable aberrations. Such molecular heterogeneity explains, in part, the disappointing performance of targeted therapeutics in unselected TNBC. Here we discuss the history of gene expression profiling in breast cancer and its application in partitioning TNBCs into subtypes that may lead to more consistent therapeutic successes in this heterogeneous disease. IMPLICATIONS FOR PRACTICE: Triple negative breast cancers (TNBCs) have historically been regarded as a single entity in clinical trial design. Over the last decade, molecular characterization has revealed much heterogeneity in TNBCs, explaining in part the lackluster performance of targeted therapeutics in TNBCs as a group. In this article, we review the history of the molecular classification of breast cancer based on gene expression profiling and discuss its role in TNBCs.