Background: Mutations in PIK3CA, the gene encoding the p110α subunit of phosphoinositide-3-kinase (PI3K), are found in approx. 25% of breast cancers. Mutations are most commonly located on one of 3 hotspot locations on exons 9 and 20 of the gene. Inhibitors of PI3K are in clinical trials and expected to be of most therapeutic benefit among tumors that possess a somatic PIK3CA mutation. Traditional screening for such mutations relies on sequencing of formalin fixed paraffin-embedded (FFPE) tumor tissue. This prospective study was performed to evaluate the concordance of ‘BEAMing’ (named after the components of the method, namely beads, emulsification, amplification and magnetics) for somatic PIK3CA mutations using circulating tumor DNA (ctDNA) extracted from peripheral blood, compared to detection of mutations via sequencing of FFPE tissue. Methods: CtDNA was extracted from the peripheral blood of 60 women with MBC and screened for the presence of a PIK3CA mutation using the BEAMing method. Tumor DNA was purified from corresponding archival patient tumor tissue and sent for sequencing of the same mutations. Primary Endpoint: concordance of PIK3CA mutational status by both methods. Results: CtDNA was successfully extracted from 60/60 patient blood samples. Adequate FFPE tissue was available from 51/60 patients. A PIK3CA mutation was detected in ctDNA of 19/60 samples, and by sequencing of FFPE tumor tissue in 14/51 samples. Among the 51 cases with matched BEAMing from blood, and sequencing from archival tumor tissue results available, concordance (mutation not detected in either sample, or same mutation detected in ctDNA and tissue) was 76.5% (39/51). Patient characteristics, prevalence of each hotspot mutation and details of discordance will be presented. Conclusions: Analysis of circulating tumor DNA for the non-invasive detection of PIK3CA mutations in patients with MBC is feasible and sensitive. Discordance may relate to change in PIK3CA status between primary and metastatic disease, emphasizing the necessity of assessing the PIK3CA status in the metastatic setting for selection of appropriate patients for clinical trials of PI3K pathway targeting agents.