Importance: Molecular aberrations in the phosphatidylinositol-3-kinase (PI3K) pathway drive tumorigenesis. Frequently co-occurring alterations in hormone receptors and/or human epidermal growth factor receptor 2 (HER2) may be relevant to mechanisms of response and resistance.

Objective: To identify patterns of aberration in the PI3K and interactive pathways that might lead to targeted therapy opportunities in clinical practice.

Design, setting, and participants: From January 2013 through December 2014, 19 784 consecutive tumor samples (>40 cancer types) were sent from thousands of clinicians in 60 countries to a single commercial laboratory for molecular profiling, including next generation sequencing, protein expression (immunohistochemical analysis [IHC]), and gene amplification (fluorescent in situ hybridization or chromogenic in situ hybridization).

Main outcomes and measures: Patterns in targetable genomic and proteomic alterations in the PI3K pathway and coincidence with hormone receptor and HER2 alterations.

Exposures: Molecular profiling across solid tumors.