Development of targeted therapies for triple-negative breast cancer: can we harness tumor heterogeneity to improve patient outcomes?

Abstract

175 ISSN 1758-1923 10.2217/BMT.13.20 © 2013 Future Medicine Ltd Breast Cancer Manage. (2013) 2(3), 175–178 Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR) and an absence of HER2 over expression. TNBC constitutes 15–20% of all breast cancers, although it is more common in young women, African–Americans and BRCA1 mutation carriers, and has an increased risk of metastatic recurrence and breast cancer-related death [1]. The poor prognosis of TNBC is related to the high likelihood of developing metastatic disease, the propensity for the involvement of visceral organs, such as the lungs and brain, with metastatic disease and the lack of effective, targeted, systemic anticancer therapies. TNBC represents a great challenge in the treatment of breast cancer despite a large body of research aimed at unraveling the biologic characteristics of TNBC and identifying those genomic features that separate it from luminal and HER2 breast cancers. Beginning with Perou et al. in 2000, gene-expression profiling has proved to be an effective tool for characterizing distinct breast cancer subtypes, including the basal-like group that segregates most closely with clinically defined TNBC [2]. This same technology was harnessed by Lehmann et al. in 2011 to further subdivide this basal-like group into six subtypes with differing patterns of dominant pathway expression [3]. This underlying hetero geneity within histopathologically defined TNBC represents a major challenge to developing more specific and effective targeted systemic therapies for TNBC, but also presents a great opportunity to develop targeted therapies with companion predictive biomarkers allowing enrichment for a responding population.