Promise and failure of targeted therapy in breast cancer

The current molecular targets in breast cancer (BC) clinical trials were identified before the advent of the genomic era and their relevance was confirmed and validated by the introduction of gene profiling. Pioneering molecular analyses and repeated data validations on different gene platforms have thus far served to define 5 subtypes of BC based on their gene signature: luminal A, luminal B, normal-like, HER2-positive, and basal. Luminal A and B tumors are estrogen receptor (ER)-positive, while basal-like are mostly negative for ER, progesterone receptor, and HER2, i.e., triple-negative. Normal-like tumors resemble normal breast tissue and the HER2 subtype is characterized by HER2 overexpression. Here, we summarize current targeted therapeutic options for the luminal, HER2-positive, and basal-like BC subtypes with respect to results observed in clinical trials as a step toward optimizing their appropriate application in the different clinical settings. We give particular consideration to the ER- and HER2-targeted therapies approved for clinical practice with respect to their merits and shortcomings in early and advanced disease, and mention the therapeutic options currently available and potentially promising for the basal-like subtype.