Tackling the diversity of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) comprises a highly diverse collection of cancers. Here, we review this diversity both in terms of gene expression subtypes and the repertoire of genetic events. Transcriptomic analyses of TNBC have revealed at least six subtypes, with the luminal androgen receptor (luminal AR) or molecular apocrine cancers forming a distinct group within triple-negative disease. Distinct from the gene expression subtypes, a diverse set of genetic events have been described in TNBC, with a number of potentially targetable genetic events found although all at relatively low frequency. Clinical trials to define the clinical utility of therapies targeting these low-frequency events will require substantial screening efforts to identify sufficient patients. Set against the diversity of TNBC, clinical studies of patients with triple-negative disease will need to be either focused on molecularly defined subsets with upfront molecular stratification, or powered for a secondary endpoint analysis of a molecularly defined subset. Such approaches will be crucial to realize the potential of precision medicine for patients with TNBCs.