PIK3CA Mutation Assessment in HR+/HER2− Metastatic Breast Cancer: Overview for Oncology Clinical Practice

Activation of the PI3K–AKT–mTOR pathway occurs in several human cancers, including hormone receptor (HR)-positive breast cancer (BC) where is associated with resistance to endocrine therapy and disease progression. In BC, most common alteration represented by PIK3CA oncogenic mutations. These mutations can occur throughout domains p110α catalytic subunit, but majority are found helical kinase (exon 9 20) that represent “hotspots”. Considering central role HR-positive inhibitors (both pan-PI3K isoform-specific) have been developed tested clinical trials. Recently, PI3Kα-selective inhibitor alpelisib was first PI3K approved for use metastatic BC based on results phase III SOLAR-1 trial. Several methods assess mutational status tumor samples validated, real-time polymerase chain reaction (PCR), digital droplet PCR (ddPCR), BEAMing assays, Sanger sequencing, next-generation sequencing (NGS) panels. new challenges will be expected once widely available a setting, harmonization testing procedures detection alterations. Herein, we provide an overview alterations discuss their determining prognosis highlight practical considerations about diagnostic activation status.