PI3K Mutation and Effect of Aspirin Use in Breast Cancer.

e23209 Background: Increasing literature suggests a protective role of aspirin in breast cancer. PI3K mutation is prevalent in 30% of estrogen receptor positive and 50% of HER2 receptor positive breast cancers. Aspirin inhibits prostaglandin-endoperoxide synthase 2 (PTGS2) through down-regulation of phosphatidylinositol 3-kinase (PI3K). A study in colorectal cancer demonstrated that regular use of aspirin was associated with superior survival among patients with PI3K mutated tumors. The aim of this study was to retrospectively examine the presence of PI3K mutation in breast cancer tissue in patients who used aspirin during treatment, and compare survival between those with and without PI3K mutations. Methods: Among 1259 patients diagnosed with breast cancer between year 2002 to 2013 at Augusta University (AU), 47 patients who used at least 81 mg of aspirin daily during cancer treatment were identified, and their breast cancer tissue blocks were analyzed for PI3K mutation by gene sequencing technique. Genomic DNAs were extracted from formalin fixed paraffin-embedded tissues using GeneRead DNA FFPE kit (Qiagen) and sequenced on Miseq sequencer (Illumina). We selectively analyzed five genes involved in the PI3K pathway, including PIK3CA, AKT, PIK3R1, PTEN, and TP53. The presence of mutation was correlated to overall survival, using Kaplan-Meier and Cox Regression analyses. Results: Of the 47 patients, 53% were Caucasian and 47% were African American. 70% were early stage (TNM stage I, II) and 30% were late stage (TNM stage III, IV). 69% were never smokers, 31% were current or former smokers. ER, PR and HER2 were expressed in 84%, 79%, and 86% patients respectively. 66% had PI3K mutation, and 34% were PI3K wild type. There was no significant difference (log-rank test p = 0.28) in overall survival (OS) of patients with PI3K mutation versus those without, although the former group had longer survival numerically. The multivariable-adjusted hazard ratio (HR) for PI3K mutation was 0.53 (p = 0.29). Conclusions: Our project supports justification for a larger study to explore the role of aspirin in prevention, treatment and prognosis of breast cancer, and to validate biomarkers such as PI3K and related genes mediating the aspirin effect.