PIK3CA: a Target or a Marker in Breast Cancers

The phosphoinositide 3 kinase (PI3K)/Akt pathway is frequently aberrantly activated in breast cancer and, basing on preclinical data, leads to cell growth and tumor proliferation. PI3K pathway activation has been suggested as a potential driver of resistance to endocrine and anti-HER2 therapies. Large genomic studies have observed that the PIK3CA gene is mutated in up to 40 % of breast cancers, mainly estrogen receptor- and HER2-positive. Some strategies targeting the PI3K/Akt/mTOR axis, in particular co-targeting the estrogen receptor and mTOR in endocrine resistant estrogen receptor-positive breast cancer, have proven successfully this hypothesis. Pan-class I PI3K inhibitors and more selective p110 alpha inhibitors are currently under investigation in different clinical settings. In this review, clinical data on the prognostic and predictive role of PIK3CA mutations in different breast cancer subtypes are covered, and a picture on the current clinical research on PI3K inhibitors is provided.