Subtyping of triple-negative breast cancer: implications for therapy

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease; gene expression analyses recently identified 6 distinct TNBC subtypes, each of which displays a unique biology. Exploring novel approaches for the treatment of these subtypes is critical, especially because the median survival for women with metastatic TNBC is less than 12 months, and virtually all women with metastatic TNBC ultimately will die of their disease despite systemic therapy. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In this review, the authors discuss recent developments in subtyping TNBC and the current and upcoming therapeutic strategies being explored in an attempt to target TNBC.

Keywords: clinical trials; subtyping triple-negative breast cancer; targeted therapies; triple-negative breast cancer.

Figure 1. Distribution of TNBC subtypes from TCGA with enriched gene ontology and potential therapeutic targets

Bargraphs display the subtype percentage relative to TNBC.

Figure 2. PI3K pathway is mutated and active in distinct TNBC subtypes

(A) Heatmap displays the PI3K pathway mutations (red) across TNBC molecular subtypes extracted from the TCGA. (B) Boxplots show protein expression levels for phosphorylated AKT (top) and negative regulators PTEN and INPP4B in non-TNBC and TNBC subtypes. Mutation and RPPA data obtained from the cBioPortal (www.cbioportal.org) on 1–12–14.