Targeted therapy for breast cancer

Breast cancer is a heterogeneous group of diseases that are clinically subdivided as hormone receptor-positive, human epidermal growth factor receptor 2-positive (HER2⁺), and triple-negative breast cancer, to guide therapeutic interventions. Agents that target estrogen receptor (ER) and HER2 are among the most successful cancer therapeutics. However, de novo or acquired resistance is common, despite the development of newer agents against these pathways. As our understanding of tumor biology improves, novel targets are being identified. Notably, inhibitors against several pathways [including, among others, the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways] have demonstrated promising activity in clinical trials, and the mTOR-inhibitor everolimus has been approved for advanced or metastatic aromatase inhibitor-resistant ER⁺ breast cancer. At present, there are no established targeted agents for triple-negative breast cancer (negative ER, progesterone receptor, and HER2). Although poly(ADP-ribose) polymerase inhibitors have shown promising activity in BRCA-related cancers, its value in the treatment of triple-negative breast cancers remains to be demonstrated. In this Review, we present a basic understanding of the major targeted agents in current practice and under development for the treatment of breast cancer in the context of the three clinical subgroups.