Abstract IA3: PI3K inhibitors in ER+ breast cancer: Next steps

Gain and loss of function mutations in the PI3 kinase pathway are extremely common in breast cancer and can be seen in all five intrinsic subtypes (Luminal A, Luminal B, HER2+, Basal-like and Claudin Low). However there is a subtype-selective spectrum of activation events including gain of kinase mutations/amplifications (e.g. PIK3CA, HER2 and AKT1) and loss of negative regulators (e.g.PTEN, INPP4B and PIK3R 1). These lesions must be matched to a large number of agents in development that target PI3K, AKT and mTOR. These agents have variable specificities, toxicities, pharmacokinetics and administration routes which affect the development of combinations with standard therapies and also with each other. In keeping with very broad clinical opportunities, positive findings in preclinical models in both luminal and basal-like breast cancer will be presented. Ongoing clinical trial designs will also be discussed and biomarker approaches for patient selection and stratification will be considered.