The role of PIK3CA mutations as a predictor of outcomes and a therapeutic target

The development of individualized therapies for the treatment of breast cancer continues to evolve at a rapid pace. Recent genome-wide efforts have uncovered new information regarding common genetic alterations that are present at high frequencies in human breast cancers. Among these, mutations in the gene encoding the p110α catalytic subunit of PI3kinase, PIK3CA, are commonly present in breast cancers, with a mutational frequency of approximately 25%. Importantly, three "hotspot" mutations comprise 80% to 90% of PIK3CA mutations, allowing for rapid analysis of tumor samples to determine the mutational status of a patient's cancer. In this article, we discuss the current views regarding the use of PIK3CA mutations as biomarkers for prognosis as well as predictors of response to therapies. We also review ongoing efforts to target mutant PIK3CA and the PI3kinase pathway and briefly discuss how mutant PIK3CA status may be useful as a predictive marker of response to these newer therapies.