Both bulk and cancer stem cell subpopulations in triple-negative breast cancer are susceptible to Wnt, HDAC, and ERα coinhibition.

Development of targeted therapies for triple-negative breast cancer (TNBC, a more aggressive subtype) is an unmet medical need. We analyzed data from 887 patients with invasive breast cancer and observed that increased Wnt and histone deacetylase (HDAC) activities are associated with estrogen receptor 1 (ESR1) and progesterone receptor (PGR) repression, poor survival, and increased relapse. The inverse correlation between Wnt signaling and repression of ESR1 and PGR expression was found to be magnified in cancer stem cell (CSC) subpopulations in TNBC cell lines.