PIK3CAMutations in Breast Cancer Subtypes Other Than HR-Positive/HER2-Negative

The phosphoinositide 3-kinase (PI3K) pathway plays a key role in cancer, influencing growth, proliferation, and survival of tumor cells. PIK3CA mutations are generally oncogenic and responsible for uncontrolled cellular growth. PI3K inhibitors (PI3Ki) can inhibit the PI3K/AKT/mTOR pathway, although burdened by not easily manageable toxicity. Among PI3Ki, alpelisib, a selective p110 alpha inhibitor, is approved for the treatment of hormone receptor (HR)+/HER2- PIK3CA mutant metastatic breast cancer (BC) that has progressed to a first line endocrine therapy. PIK3CA mutations are also present in triple negative BC (TNBC) and HER2+ BC, although the role of PI3K inhibition is not well established in these subtypes. In this review, we go through the PI3K/AKT/mTOR pathway, describing most common mutations found in PI3K genes and how they can be detected. We describe the available biological and clinical evidence of PIK3CA mutations in breast cancers other than HR+/HER2-, summarizing clinical trials investigating PI3Ki in these subtypes.

Automated summary

The PI3K pathway plays a key role in cancer, and PIK3CA mutations are common in breast cancer. The role of PI3K inhibition in different breast cancer subtypes is not well established. Alpelisib is an effective drug for treating breast cancer with specific mutations. This review summarizes the clinical evidence of PIK3CA mutations in different breast cancer subtypes and the clinical trials investigating PI3Ki.