Therapeutic management of metastatic breast cancers is drastically changing. Recent evidence from extensive prospective clinical studies has demonstrated the efficacy of treatments combining endocrine therapies and other targeted therapies, which now become standard treatments.
Among these targeted therapies, the PI3K-AKT-mTOR pathway inhibition is the treatment of choice in a progressive disease under endocrine therapy. More recently, the association with CDK4/6 inhibitors is progressively becoming a treatment of choice for hormone-dependent metastatic cancers.
Despite recent advances in precision medicine, the known activating mutations of PIK3CA gene, as well as CCND1 gene amplifications or p16 gene losses, are not associated with response to treatments using inhibitors of these pathways. Moreover, subtypes of breast tumors that do not express hormone receptors and HER2 protein (triple negative subtype), are challenging tumors as endocrine and targeted therapies are non effective.
For these reasons, it is mandatory to identify new targets and predictive biomarkers to better select patients and thus prescribe adapted and targeted therapies.