Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival.
Level 3 - non-randomized controlled study
Prospective cohort study analyzing survival outcomes by biomarker status without randomized treatment assignment.
PubMed 23094721 · doi:10.1056/NEJMoa1207756
What was done
Researchers analyzed data from 964 patients with colon or rectal cancer from the prospective Nurses' Health Study and Health Professionals Follow-up Study. Tumor specimens were evaluated for PIK3CA mutation status and other molecular markers (PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation). Multivariate Cox proportional-hazards models assessed the association between regular postdiagnosis aspirin use and colorectal cancer-specific survival and overall survival, stratified by PIK3CA mutation status.
What was found
Among patients with mutated-PIK3CA colorectal cancer, regular postdiagnosis aspirin use was associated with improved colorectal cancer-specific survival (multivariate hazard ratio for cancer-related death 0.18; 95% CI, 0.06 to 0.61; P<0.001) and overall survival (multivariate hazard ratio for death from any cause 0.54; 95% CI, 0.31 to 0.94; P=0.01). In contrast, among patients with wild-type PIK3CA, aspirin use was not associated with colorectal cancer-specific survival (multivariate HR 0.96; 95% CI, 0.69 to 1.32; P=0.76; P=0.009 for interaction) or overall survival (multivariate HR 0.94; 95% CI, 0.75 to 1.17; P=0.96; P=0.07 for interaction).
Why it matters
This suggests tumor PIK3CA mutation status may serve as a predictive molecular biomarker to identify colorectal cancer patients likely to benefit from adjuvant aspirin therapy.
Limits
The study is observational and not randomized, raising the potential for residual confounding. Aspirin exposure was self-reported, and the study population was restricted to health professionals, which may limit generalizability. The abstract does not report exact numbers of patients within the mutated versus wild-type PIK3CA subgroups.
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