Clinical Implications of Mutations in the PI3K Pathway in HER2+ Breast Cancer: Prognostic or Predictive?

Recent advances in tumor genetics and drug development have led to the generation of a wealth of anti-cancer-targeted therapies. These drugs aim at targeting a particular vulnerability in the tumor generated in most cases as a result of dependence on an oncogene and/or loss of a tumor suppressor. Genes in the phosphoinositide 3-kinase (PI3K)/AKT pathway are the most frequently altered in human cancers. Aberrant activation of the PI3K/AKT pathway has been shown to confer resistance to HER2-targeted therapies. Several drugs targeting PI3K/ATK have been developed and are currently in clinical trials in different phases of clinical development, alone or in combination. The impact of mutations in the phosphoinositide 3-kinase (PI3K)/AKT pathway in HER2-amplified breast cancers will be the focus of this review.